The Role of Nanoparticles in Pharmaceuticals: A Comprehensive Review

Introduction

Nanotechnology has emerged as one of the most promising and transformative fields in science and medicine, with nanoparticles (NPs) at the forefront of this revolution. Nanoparticles, defined as particles with dimensions ranging from 1 to 100 nanometers, exhibit unique physicochemical properties that differ significantly from those of bulk materials. These properties, including increased surface area, high reactivity, and the ability to be easily functionalized, make nanoparticles ideal candidates for various applications in the pharmaceutical industry [1]. In recent years, the role of nanoparticles in pharmaceuticals has expanded rapidly, encompassing drug delivery, diagnostics, imaging, gene therapy, and the treatment of diseases that were previously difficult to address [2,3]. This growth has opened new avenues for enhancing drug efficacy, reducing side effects, and improving the quality of patient care [4]. The pharmaceutical industry faces numerous challenges, such as poor bioavailability of certain drugs, toxicity, the inability to target specific tissues, and high treatment costs [5,6]. Nanoparticles, by virtue of their small size and tunable surface characteristics, offer potential solutions to these issues.

One of the major challenges in drug development is the low solubility of many drugs, particularly those in the class of hydrophobic compounds. Nanoparticles can improve the solubility and stability of these compounds, making them more effective in treating diseases [7,8]. Furthermore, the ability to modify the surface of nanoparticles allows for the development of drug delivery systems that can target specific cells, tissues, or organs, improving the precision and efficiency of treatments. This targeted approach reduces the need for high drug doses, thereby minimizing potential side effects and improving patient compliance [9,10]. A major advantage of nanoparticles in pharmaceuticals is their ability
 to improve the bioavailability of poorly water-soluble drugs. Many conventional drugs suffer from limited bioavailability due to their low solubility in the gastrointestinal tract. Nanoparticles can overcome this limitation by encapsulating the drugs in carrier systems that enhance their dissolution rate, facilitating absorption into the bloodstream [11]. This is particularly crucial for drugs that require a high concentration at the site of action, such as anticancer agents and anti-inflammatory drugs [12]. Moreover, nanoparticles can also enable the sustained or controlled release of drugs, which helps maintain therapeutic drug levels over extended periods.

This feature of nanoparticles reduces the frequency of drug administration and can significantly enhance the therapeutic outcomes, especially for chronic diseases such as diabetes or cardiovascular diseases [13,14]. Another critical aspect of nanoparticles is their potential in overcoming multidrug resistance (MDR), a significant challenge in cancer therapy. MDR occurs when cancer cells become resistant to the effects of chemotherapy drugs, leading to treatment failure. Nanoparticles can be engineered to deliver chemotherapy drugs directly to the tumor cells, bypassing the mechanisms of drug resistance. Additionally, nanoparticles can be functionalized with molecules that inhibit drug efflux pumps, which are responsible for pumping the drugs out of cancer cells [15,16]. By enhancing the drug's ability to remain within the cancer cells, nanoparticles can increase the drug's cytotoxicity and improve the overall therapeutic effect [17]. In addition to drug delivery, nanoparticles have shown great promise in diagnostics and imaging, providing valuable tools for early disease detection and monitoring. Nanoparticles can be engineered to carry imaging agents such as fluorescent dyes, magnetic particles, or radioactive isotopes, making them ideal for use in various imaging modalities, including magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) [18,19].

These nanoparticles not only improve the resolution and contrast of the images but also allow for targeted imaging, where the nanoparticles accumulate at specific disease sites, such as tumors or inflammatory areas. This targeted approach enhances the precision of diagnostic imaging, enabling earlier detection and more accurate monitoring of disease progression or treatment efficacy [20]. Nanoparticles are also being explored for gene therapy, where they serve as carriers for delivering nucleic acids, such as DNA or RNA, into target cells. This is particularly important for genetic disorders, where the delivery of functional genes can correct defective ones [21]. Nanoparticles, such as lipid nanoparticles (LNPs) or dendrimers, are ideal candidates for gene delivery because they can protect the genetic material from degradation by nucleases and facilitate its uptake into cells. Recent advancements in RNA-based therapies, such as messenger RNA (mRNA) vaccines, have demonstrated the potential of nanoparticles in delivering therapeutic genes or vaccines [22]. The success of COVID-19 mRNA vaccines developed using lipid nanoparticles has highlighted the power of nanoparticles in revolutionizing not only drug delivery but also vaccine development [23]. The use of nanoparticles in pharmaceuticals also extends to the treatment of infectious diseases. Antibacterial, antiviral, and antifungal nanoparticles have been studied for their ability to target pathogens directly. Silver nanoparticles, for example, have well-documented antimicrobial properties and are being incorporated into wound dressings, medical devices, and topical creams to prevent infections [24].

The antimicrobial properties of nanoparticles stem from their ability to interact with the microbial cell membrane, disrupt cellular functions, and induce oxidative stress, leading to the death of the pathogen. Moreover, nanoparticles can be engineered to deliver antimicrobial agents more efficiently, ensuring that the drug reaches the site of infection at an optimal concentration [25]. Despite the promising potential of nanoparticles in pharmaceuticals, their application is not without challenges. One of the primary concerns is the potential toxicity of nanoparticles, as their small size allows them to interact with biological systems in ways that larger particles do not. The toxicity of nanoparticles depends on factors such as their size, shape, surface charge, and material composition. The fate of nanoparticles within the body, their biodistribution, and their long-term effects on organs and tissues need to be thoroughly understood before their widespread use in clinical settings [26]. Regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are working to establish clear guidelines for the approval and monitoring of nanoparticle based drugs, ensuring their safety and efficacy in human patients [27,28].

Additionally, the manufacturing and scalability of nanoparticle- based drug delivery systems remain challenges that need to be addressed. While laboratory-scale production of nanoparticles has been well established, scaling up the production process for commercial use requires the development of cost-effective and reproducible manufacturing methods. Furthermore, the complex nature of nanoparticle formulations, including their size, shape, and surface modifications, requires rigorous quality control measures to ensure consistency across batches [29,30]. Advances in nanomaterial synthesis, surface modification techniques, and formulation design are essential to overcome these challenges and bring nanoparticle-based drugs to market. The role of nanoparticles in pharmaceuticals is vast and multifaceted, offering significant potential to transform drug delivery, diagnostics, and therapy. From enhancing the solubility and bioavailability of drugs to enabling targeted and controlled release, nanoparticles have the ability to improve the therapeutic outcomes of many drugs [31]. Their applications extend beyond drug delivery to include diagnostics, imaging, gene therapy, and the treatment of infectious diseases [32].

Various Types of Nanoparticles Used in Pharmaceuticals

Nanoparticles (NPs) have gained significant attention in pharmaceutical applications due to their unique properties and versatile behavior. These properties, such as high surface-to-volume ratio, ease of surface functionalization, and ability to interact at the cellular level, allow nanoparticles to serve as effective drug carriers, therapeutic agents, and diagnostic tools. Several types of nanoparticles have been explored for their potential in drug delivery, cancer treatment, gene therapy, and other biomedical applications. The types of nanoparticles used in pharmaceuticals can be broadly classified into polymeric nanoparticles, lipid-based nanoparticles, inorganic nanoparticles, and biological nanoparticles, each with its distinct advantages and applications.

Polymeric Nanoparticles
Polymeric nanoparticles are one of the most widely studied types of nanoparticles in pharmaceuticals. They are made from biodegradable and biocompatible polymers, making them ideal for drug delivery applications. These nanoparticles can be designed for controlled or sustained release, improving the bioavailability and therapeutic efficacy of drugs [33]. Common materials used to prepare polymeric nanoparticles include poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA), and chitosan, all of which are FDA-approved for medical use [34,35]. PLGA-based nanoparticles are particularly popular due to their biodegradability and ability to encapsulate a wide range of hydrophilic and hydrophobic drugs. The ability to tune the degradation rate of PLGA particles allows for the controlled release of the encapsulated drug over a prolonged period, which is highly beneficial for the treatment of chronic diseases such as cancer or diabetes [36,37]. Polymeric nanoparticles also offer the advantage of surface modification, which can enhance drug targeting. Functionalizing the surface with ligands, antibodies, or peptides enables nanoparticles to selectively bind to specific receptors on target cells, such as cancer cells or immune cells, thus improving the specificity and reducing the side effects of the treatment [38]. Additionally, polymeric nanoparticles can be used to deliver both small molecule drugs and large biomolecules like proteins, peptides, and nucleic acids [39,40]. These features make polymeric nanoparticles highly versatile in the pharmaceutical industry.

Lipid-Based Nanoparticles
Lipid-based nanoparticles, such as liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs), have become prominent candidates for drug delivery applications due to their biocompatibility, ease of preparation, and ability to encapsulate both hydrophilic and hydrophobic drugs [41,42]. Among lipid nanoparticles, liposomes are the most widely used. Liposomes are spherical vesicles made from lipid bilayers that can encapsulate drugs in their aqueous core or within the lipid bilayer itself [43]. Liposomes can be engineered to improve their stability, prolong circulation time, and target specific cells or tissues. For instance, pegylated liposomes, which are coated with polyethylene glycol (PEG), can evade the immune system, resulting in longer systemic circulation times [44]. This makes liposomes suitable for delivering chemotherapeutic agents, vaccines, and gene therapy [45]. Solid lipid nanoparticles (SLNs) are another type of lipid- based nanoparticle that has gained popularity due to their ability to provide controlled release of the encapsulated drug. SLNs are composed of solid lipids, and their production process involves melting the lipid matrix and dispersing it in an aqueous phase [46]. SLNs offer advantages such as improved stability compared to liposomes and the ability to deliver both lipophilic and hydrophilic drugs [47]. Nanostructured lipid carriers (NLCs), a further advancement of SLNs, consist of a blend of solid and liquid lipids, offering improved drug loading capacity and better release profiles [48]. NLCs are particularly effective in delivering poorly water- soluble drugs and have shown promising results in topical and oral drug delivery [49].

 Inorganic Nanoparticles
Inorganic nanoparticles, such as gold nanoparticles (AuNPs), silica nanoparticles, and magnetic nanoparticles, are extensively used in pharmaceutical applications for drug delivery, imaging, and therapeutic purposes [50]. Gold nanoparticles, due to their biocompatibility and ease of functionalization, are widely used for drug delivery and diagnostic applications [51]. AuNPs can be easily modified with various biomolecules, including antibodies, peptides, and nucleic acids, to achieve targeted drug delivery to specific cells or tissues [52]. Additionally, gold nanoparticles exhibit excellent optical properties that allow them to be used as imaging agents in diagnostic applications, such as surface enhanced Raman scattering (SERS) or in vitro imaging [53]. Their ability to absorb and scatter light makes them ideal candidates for applications in photothermal therapy, where localized heating is used to destroy cancer cells [54]. Silica nanoparticles are another class of inorganic nanoparticles that have gained interest in drug delivery due to their high surface area and customizable pore structure. Mesoporous silica nanoparticles (MSNs) are particularly well-suited for drug delivery because their pores can be loaded with a variety of therapeutic agents, including small molecules, proteins, and nucleic acids. MSNs can be functionalized to achieve targeted delivery and controlled release, making them suitable for cancer therapy and gene delivery [55]. Additionally, the surface of silica nanoparticles can be modified to enhance their stability, prevent premature drug release, and improve their circulation time [56]. Magnetic nanoparticles, typically composed of iron oxide (Fe3O4) or iron oxide based materials, have gained significant attention for their role in drug delivery, diagnostics, and hyperthermia treatment [57]. Magnetic nanoparticles can be manipulated using an external magnetic field, allowing for precise targeting and localization of drug delivery at specific sites in the body [58]. Moreover, these nanoparticles can be used in magnetic resonance imaging (MRI) to enhance the contrast of images, helping clinicians visualize tumors or other abnormal tissues [59]. The use of magnetic nanoparticles in hyperthermia treatment involves the application of an alternating magnetic field, which induces localized heating in the nanoparticles, thereby destroying cancer cells [60].

Biological Nanoparticles
Biological nanoparticles, such as exosomes and virus-like particles (VLPs), have emerged as a promising class of nanoparticles for drug delivery and gene therapy. Exosomes are small vesicles secreted by various cell types that have natural properties enabling them to transport biomolecules, including proteins, lipids, and RNA, to other cells. These nanoparticles have been explored for their potential to deliver RNA-based therapeutics and for their ability to target specific tissues [61]. Exosomes can be engineered to carry drugs or therapeutic molecules and can serve as both drug carriers and delivery vehicles for gene therapy [62]. Their natural origin and biocompatibility make them ideal candidates for minimizing immunogenicity and improving therapeutic efficacy. Virus-like particles (VLPs) are non-infectious viral particles that resemble the structure of a virus but lack the viral genome. VLPs have gained attention for their ability to deliver nucleic acids in gene therapy applications [63]. These particles can encapsulate large amounts of genetic material and protect it from degradation, improving the efficiency of gene transfer into target cells. VLPs can be engineered to target specific cells or tissues, offering a highly specific and effective means of gene delivery [64]. The types of nanoparticles used in pharmaceuticals, such as polymeric nanoparticles, lipid-based nanoparticles, inorganic nanoparticles, and biological nanoparticles, each have distinct advantages depending on the therapeutic goal. Polymeric nanoparticles are valued for their biodegradability and controlled drug release, while lipid-based nanoparticles like liposomes and solid lipid nanoparticles excel in drug encapsulation and targeted delivery. Inorganic nanoparticles, such as gold, silica, and magnetic nanoparticles, offer additional functionality in drug delivery, imaging, and treatment. Biological nanoparticles like exosomes and VLPs provide unique, biocompatible delivery systems with natural targeting capabilities. As research in nanomedicine continues to evolve, these nanoparticles hold great promise in revolutionizing the treatment of a wide range of diseases, from cancer to infectious diseases, by improving drug bioavailability, targeting specificity, and therapeutic outcomes[65].

 Drug Delivery Systems

Nanoparticles provide an effective means to deliver drugs with greater precision, improving their bioavailability, solubility, and targeting ability.

Increased Drug Solubility: Many poorly water-soluble drugs can benefit from nanoparticle formulations, which enhance solubility and absorption. Nanoparticles, particularly those made from lipids or polymers, can encapsulate drugs, improving their dispersion in aqueous solutions [1,2].

Targeted Delivery: Nanoparticles can be engineered to target specific cells or tissues, improving the therapeutic index of drugs by reducing off-target effects. Surface modification of nanoparticles with targeting ligands (e.g., antibodies or peptides) allows them to recognize and bind to specific receptors on the target cell surfaces, enhancing the precision of drug delivery [3,4].

Controlled Release: Nanoparticles can be designed to provide controlled or sustained release of drugs over extended periods. This controlled release minimizes the fluctuations in drug concentration, improving therapeutic outcomes while reducing side effects [5].

Nanoparticles (NPs) are revolutionizing the field of drug delivery systems due to their unique properties that enable them to enhance the bioavailability, stability, and controlled release of therapeutic agents. Their small size, large surface area, and ease of surface modification make them excellent candidates for targeting specific tissues or cells, improving the pharmacokinetics of drugs, and reducing systemic toxicity. Various types of nanoparticles, such as polymeric nanoparticles, liposomes, solid lipid nanoparticles (SLNs), dendrimers, and inorganic nanoparticles, are widely explored in drug delivery, each providing specific advantages for different therapeutic applications.

Polymeric nanoparticles are among the most commonly utilized carriers in drug delivery systems because of their biocompatibility, biodegradability, and ability to provide controlled and sustained drug release. These nanoparticles are typically composed of biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA), polycaprolactone (PCL), and chitosan. Their main advantage lies in the ability to encapsulate both hydrophobic and hydrophilic drugs, offering flexibility for various therapeutic applications [66,67]. For example, PLGA-based nanoparticles have been successfully employed for the controlled release of anticancer drugs like paclitaxel and doxorubicin, allowing for prolonged drug action and reduced side effects compared to traditional chemotherapy [68]. Polymeric nanoparticles can also be surface-modified with ligands or antibodies to improve their targeting capabilities. This ability allows for selective drug delivery to specific cells or tissues, which is particularly useful in treating localized diseases like cancer. The surface modification of polymeric nanoparticles with folic acid, transferrin, or monoclonal antibodies has shown great promise in achieving tumor-specific targeting and enhancing therapeutic outcomes [69]. Furthermore, the surface of these nanoparticles can be functionalized with polymers like polyethylene glycol (PEG) to improve their circulation time in the bloodstream, reducing their clearance by the reticuloendothelial system and improving the pharmacokinetics of the encapsulated drug [70,71].

Liposomes are vesicular structures composed of one or more phospholipid bilayers, capable of encapsulating both hydrophilic and hydrophobic drugs within their aqueous core or lipid bilayer. Liposomes have been extensively used in drug delivery systems due to their ability to deliver a wide range of therapeutic agents, including chemotherapeutics, antibiotics, and vaccines [72]. One of the key advantages of liposomes is their ability to protect encapsulated drugs from degradation in the bloodstream, thereby increasing the stability and bioavailability of the drugs. Furthermore, liposomes can be engineered to target specific cells or tissues by incorporating targeting ligands into the lipid bilayer, such as monoclonal antibodies, peptides, or small molecules. This targeting ability allows for enhanced drug delivery to tumor cells, immune cells, or endothelial cells, which significantly improves the therapeutic efficacy while minimizing off-target side effects [73]. Solid lipid nanoparticles (SLNs) are another lipid-based system used in drug delivery. These nanoparticles are composed of solid lipids, and their preparation method involves the dispersion of a lipid matrix in an aqueous phase, followed by solidification at room temperature. SLNs offer several advantages, such as controlled release, stability, and the ability to incorporate both lipophilic and hydrophilic drugs [74].
Additionally, SLNs can be modified for targeted drug delivery by functionalizing their surface with specific ligands. They have been used for the controlled release of drugs like anticancer agents and antibiotics, as well as for the treatment of skin diseases due to their ability to penetrate the skin barrier [75]. Nanostructured lipid carriers (NLCs), an advanced form of SLNs, are composed of a mixture of solid and liquid lipids, which helps to improve the loading capacity of drugs and their release profiles. NLCs offer the advantages of better drug solubility, enhanced stability, and reduced drug expulsion during storage. These properties make NLCs particularly suitable for the delivery of poorly water-soluble drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs) and anticancer agents [76,77]. The controlled release characteristics of NLCs can be fine-tuned by modifying the lipid composition and the preparation conditions, allowing for the sustained release of drugs over extended periods. Dendrimers are highly branched, tree-like macromolecules with a well-defined structure. Due to their small size, high surface area, and the availability of functional groups on their surface, dendrimers offer several advantages in drug delivery applications. Their unique architecture allows for the encapsulation of both small molecule drugs and larger biomolecules like proteins and nucleic acids. Dendrimers can be synthesized from various materials, including polyamidoamine (PAMAM), polyester, and polypropylene imine (PPI), each offering distinct features in terms of drug loading, release, and biocompatibility [78,79].

The surface functionalization of dendrimers with targeting ligands or polyethylene glycol (PEG) can further enhance their drug delivery capabilities, enabling specific targeting to tumor cells, immune cells, or other disease sites. Dendrimers have been explored for delivering a wide range of drugs, including anticancer agents, antibiotics, and gene therapy. For example, PAMAM dendrimers have been utilized for the delivery of anticancer drugs like paclitaxel, where they serve as carriers to improve drug solubility and facilitate controlled release [80]. Additionally, dendrimers can also be used for gene delivery, as they can efficiently bind to nucleic acids like DNA or RNA and protect them from degradation, improving the efficacy of gene therapy [81]. The multivalency of dendrimers, with numerous functional groups available for conjugation, makes them ideal carriers for combination therapies, where multiple drugs can be delivered simultaneously. Inorganic nanoparticles, such as gold nanoparticles (AuNPs), silica nanoparticles, and magnetic nanoparticles, have gained significant attention in drug delivery due to their unique properties, including high surface area, stability, and ease of functionalization. Gold nanoparticles (AuNPs) are widely studied for drug delivery because of their biocompatibility, ease of synthesis, and ability to conjugate with various biomolecules, such as antibodies, peptides, and nucleic acids.

AuNPs have been used for the delivery of small molecule drugs, gene therapy agents, and even for cancer treatment via photothermal therapy. The surface of AuNPs can be functionalized with targeting ligands to improve their specificity toward cancer cells or other disease sites, thereby enhancing therapeutic outcomes [82,83]. Silica nanoparticles, particularly mesoporous silica nanoparticles
 
(MSNs), have shown promise in drug delivery due to their tunable pore size, high surface area, and ability to load a wide variety of drugs. MSNs can encapsulate hydrophobic drugs, proteins, and nucleic acids within their pores, and their surface can be modified to control the release profile of the encapsulated drug. MSNs have been explored for controlled release drug delivery, gene therapy, and even imaging applications. Their biocompatibility and ease of modification make them a versatile choice for targeted drug delivery systems [84,85]. Magnetic nanoparticles, typically composed of iron oxide, have also found use in drug delivery, particularly for targeting and localized treatment. These nanoparticles can be guided to specific sites using an external magnetic field, allowing for the precise delivery of drugs to tumors or other diseased tissues. Magnetic nanoparticles have been utilized in hyperthermia therapy, where the nanoparticles are heated by an alternating magnetic field to kill cancer cells. They are also used in imaging techniques, such as magnetic resonance imaging (MRI), to enhance tumor detection and localization [86,87].

Nanoparticles in Diagnostics and Imaging

Nanoparticles (NPs) are increasingly playing a crucial role in diagnostics and medical imaging due to their unique physicochemical properties, including high surface area, ease of functionalization, and the ability to interact with biological systems at the molecular level. These properties enable NPs to be used as contrast agents, biomarkers, and platforms for targeted molecular imaging, facilitating more accurate disease detection, monitoring, and personalized treatment strategies. The incorporation of nanoparticles into diagnostic and imaging modalities such as magnetic resonance imaging (MRI), computed tomography (CT), ultrasound, positron emission tomography (PET), and optical imaging has revolutionized the medical field by improving both the sensitivity and specificity of these technologies.

Nanoparticles as Contrast Agents in Imaging
One of the most widely explored applications of nanoparticles in imaging is as contrast agents for different imaging modalities. For example, in magnetic resonance imaging (MRI), iron oxide nanoparticles, particularly superparamagnetic iron oxide nanoparticles (SPIONs), are commonly used as contrast agents. These NPs create strong magnetic fields that affect the relaxation time of water protons, enhancing the contrast between healthy and diseased tissues. SPIONs are highly biocompatible and can be surface-modified with various targeting ligands (e.g., peptides, antibodies, and folic acid) to improve their specificity towards particular tissues, such as tumors or inflammation sites. SPIONs have demonstrated significant potential in improving the diagnostic accuracy of MRI, especially in the detection of cancer and inflammatory diseases [87,88]. Gold nanoparticles (AuNPs) are another prominent type of nanoparticle used as contrast agents, particularly in X-ray and computed tomography (CT) imaging. Their high atomic number and excellent electron density enable them to absorb X-rays efficiently, providing enhanced contrast in CT imaging. Gold nanoparticles can also be conjugated with targeting molecules, such as monoclonal antibodies, to deliver contrast selectively to tumors or other diseased tissues, allowing for early detection and more precise imaging [89,90]. Additionally, AuNPs offer significant advantages in optical imaging techniques, such as surface-enhanced Raman spectroscopy (SERS), due to their unique ability to enhance Raman scattering signals. SERS- based imaging using AuNPs can detect biomolecular interactions and biomarkers with high sensitivity, making it a powerful tool for the early diagnosis of diseases like cancer, viral infections, and neurodegenerative diseases [91,92].

Nanoparticles in Positron Emission Tomography (PET) and Single-Photon Emission Computed Tomography (SPECT) Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are advanced imaging techniques that are widely used for in vivo diagnostics, particularly in oncology, cardiology, and neurology. Nanoparticles are utilized in these imaging techniques as radiolabeled agents, allowing for non-invasive imaging of physiological processes at the molecular level. Polymeric nanoparticles and liposomes have been designed to carry radioactive isotopes, such as fluorine-18, iodine-131, and technetium-99m, for PET and SPECT imaging. The advantage of using NPs in these modalities is their ability to encapsulate radioactive molecules, which improves the pharmacokinetics and biodistribution of the radiotracers, ensuring prolonged circulation time and targeted delivery to specific tissues [93,94]. For example, lipid-based nanoparticles (LNPs), particularly liposomes, have been used for the delivery of radiolabeled compounds for tumor imaging. The liposomal formulation improves the accumulation of radiotracers in tumor tissues through the enhanced permeability and retention (EPR) effect, which allows for more accurate tumor detection with PET or SPECT. Moreover, the surface of these nanoparticles can be functionalized with targeting ligands, such as antibodies or peptides, which selectively bind to tumor markers, enhancing the specificity of imaging and facilitating early diagnosis [95,96]. Gold nanoparticles have also been explored in PET and SPECT imaging due to their ability to carry a wide range of radioactive isotopes, such as copper-64 (for PET) and technetium-99m (for SPECT).
The high surface area of gold nanoparticles allows for the attachment of multiple radiolabels, increasing the sensitivity and resolution of the imaging. When combined with targeting moieties, AuNPs can be directed toward specific tumor cells or tissues, providing a non-invasive means of visualizing cancer cells and tracking disease progression [97,98].

Nanoparticles in Optical Imaging
Optical imaging techniques, such as fluorescence imaging, bioluminescence imaging, and Raman spectroscopy, have gained significant attention in the field of diagnostics due to their non- invasive nature, high resolution, and real-time monitoring capabilities. Quantum dots (QDs) are semiconductor nanoparticles that have emerged as powerful tools in optical imaging. These nanoparticles exhibit unique optical properties, such as size- dependent fluorescence emission, allowing for multiplexed imaging of multiple targets simultaneously. QDs can be conjugated with biomolecules like antibodies, peptides, or small molecules to specifically target cells or tissues of interest. Due to their high photostability and narrow emission spectra, QDs provide superior performance in imaging applications, such as cancer detection, cell tracking, and biomarker profiling [99,100]. Carbon nanotubes (CNTs) are another class of nanoparticles that have shown promise in optical imaging due to their fluorescent properties. CNTs can be functionalized with specific biomolecules for targeted imaging of cancer cells, bacterial infections, and other disease markers. Their high surface area and ease of modification make them ideal candidates for imaging applications in early diagnostics, especially when combined with other imaging techniques like MRI and fluorescence [101,102]. Additionally, CNTs can also be used in photoacoustic imaging (PAI), where their unique optical absorption properties enable high-resolution imaging of deep tissues. Another promising optical imaging technique is Raman spectroscopy, which is often coupled with nanoparticles like AuNPs or silver nanoparticles (AgNPs) for surface-enhanced Raman spectroscopy (SERS). SERS provides an ultra-sensitive and highly specific method for detecting biomolecules at the single-molecule level. The use of metallic nanoparticles, particularly AuNPs, significantly enhances the Raman scattering signals, making it possible to detect even trace amounts of disease biomarkers in body fluids or tissues. SERS-based imaging has been used for early detection of cancer, bacterial infections, and even for monitoring the efficacy of therapeutic treatments [103,104].

Nanoparticles in Targeted Diagnostics and Theranostics Nanoparticles are increasingly being explored for theranostic applications, which combine both therapeutic and diagnostic functions in a single platform. By integrating diagnostic imaging agents and therapeutic payloads into a single nanoparticle, theranostic nanoparticles enable real-time monitoring of treatment efficacy and disease progression, offering a more personalized approach to patient care. For example, NPs like liposomes and polymeric nanoparticles have been designed to carry both imaging agents and anticancer drugs, allowing for simultaneous tumor imaging and targeted drug delivery. This combination can significantly enhance the precision of cancer treatments by ensuring that the drug is delivered specifically to the tumor site and by enabling the monitoring of treatment responses in real time [105,106]. Magnetic nanoparticles (MNPs) have also been used in theranostic applications, particularly in cancer imaging and therapy. MNPs can be functionalized with anticancer drugs and used for both imaging via MRI and therapeutic purposes through hyperthermia (by applying an external magnetic field to induce heat). The ability to combine diagnosis and therapy in one nanoparticle system not only improves the accuracy of disease detection but also reduces the number of treatments a patient needs, ultimately improving therapeutic outcomes [107,108].

Nanoparticles in Therapeutic Applications

Nanoparticles (NPs) have revolutionized therapeutic applications across a wide range of medical fields, offering numerous advantages over conventional drug delivery systems. These include enhanced bioavailability, improved pharmacokinetics, reduced systemic toxicity, and the ability to target specific cells or tissues with high precision. The unique size, surface area, and physicochemical properties of nanoparticles make them ideal candidates for drug delivery, gene therapy, vaccine development, and cancer therapy, among other therapeutic applications. Nanoparticles can be engineered to encapsulate a variety of therapeutic agents, including small molecules, proteins, nucleic acids, and even vaccines, and can be designed for controlled release, ensuring the sustained release of the active pharmaceutical ingredient at the site of action.

Nanoparticles in Drug Delivery Systems
Nanoparticles play a critical role in improving the delivery of drugs to their target sites, increasing therapeutic efficacy while minimizing side effects. The ability to encapsulate hydrophobic and hydrophilic drugs within a single nanoparticle platform has been a breakthrough in drug formulation, especially for poorly soluble drugs. Polymeric nanoparticles (PNPs) and liposomes are widely used in drug delivery due to their ability to encapsulate a variety of drugs and control their release over time. Polymeric nanoparticles offer advantages such as tunable degradation rates and biocompatibility, making them suitable for controlled drug release applications in cancer, inflammation, and other diseases. The surface of these nanoparticles can be functionalized with targeting ligands, such as antibodies or peptides, enabling them to specifically target disease sites, such as tumors or infected tissues [109,110].

Liposomes, which are spherical vesicles composed of lipid bilayers, are another widely used type of nanoparticle for drug delivery. They have been extensively studied for their ability to carry both hydrophobic and hydrophilic drugs, providing an excellent platform for the delivery of chemotherapy agents, vaccines, and anti-inflammatory drugs. Liposomes can encapsulate drugs, protecting them from degradation, and they can be engineered to release the drug in a controlled manner. By modifying the surface of liposomes with polyethylene glycol (PEG) or other targeting molecules, their circulation time can be extended, and they can be directed towards specific cells or tissues, thus improving therapeutic outcomes [111,112].

Nanostructured lipid carriers (NLCs) are another class of nanoparticles used in drug delivery systems. NLCs are composed of a mixture of solid and liquid lipids, offering improved stability compared to traditional liposomes and the ability to deliver both hydrophilic and lipophilic drugs. These nanoparticles have shown promise in the delivery of anticancer agents, anti-inflammatory drugs, and peptides, as they offer enhanced drug entrapment efficiency and controlled release profiles. The ability to modify the surface of NLCs with targeting moieties further enhances their specificity, allowing for targeted therapy in diseases like cancer [113,114].

 Nanoparticles in Gene Therapy
Gene therapy aims to treat or prevent disease by introducing genetic material into a patient's cells to correct defective genes or regulate the expression of genes. Nanoparticles have emerged as one of the most effective vehicles for delivering genetic material such as DNA, RNA, or gene-editing tools like CRISPR/Cas9. The small size, biocompatibility, and ease of functionalization of nanoparticles make them ideal candidates for gene delivery applications. Polymeric nanoparticles and lipid nanoparticles (LNPs) have shown great potential in delivering nucleic acids into cells, improving the efficiency of gene transfer while minimizing side effects [115,116].

Lipid nanoparticles (LNPs) are particularly significant in the context of RNA-based therapies, such as mRNA vaccines and RNA interference (RNAi). LNPs are used to encapsulate and protect mRNA molecules, preventing their degradation by nucleases and ensuring their efficient delivery to target cells. This platform played a pivotal role in the development of mRNA vaccines for COVID19, demonstrating the ability of nanoparticles to deliver RNA vaccines with high efficiency. Moreover, LNPs have been explored for the delivery of gene-editing tools, such as CRISPR/ Cas9, offering targeted gene modification in diseases like sickle cell anemia and cystic fibrosis [117,118].

In addition to LNPs, polymeric nanoparticles (PNPs) and dendrimers have also been investigated for gene delivery. These nanoparticles can be modified with various cationic groups to facilitate the electrostatic binding of negatively charged nucleic acids, promoting cellular uptake. Polymeric nanoparticles can be designed to release their payloads in response to specific stimuli, such as changes in pH or temperature, providing control over gene delivery and expression. Dendrimers, with their well-defined structure and high surface area, can also be used for gene delivery, offering the ability to carry large amounts of genetic material and target specific tissues or organs [119,120].

Nanoparticles in Cancer Therapy
Cancer therapy has greatly benefited from the use of nanoparticles, particularly in the form of targeted drug delivery systems. Nanoparticles can be engineered to carry chemotherapy drugs, gene therapies, or immunotherapies directly to the tumor site, thus enhancing the therapeutic effect while minimizing toxicity to surrounding healthy tissues. Polymeric nanoparticles, liposomes, and dendrimers have been widely investigated for their ability to deliver anticancer drugs, such as doxorubicin, paclitaxel, and cisplatin, with improved bioavailability and controlled release. For example, liposomal formulations of anticancer drugs, such as Doxil®® (liposomal doxorubicin), have shown significant improvements in the treatment of cancers like breast cancer, ovarian cancer, and Kaposi’s sarcoma. Liposomes protect the encapsulated drug from premature degradation, reduce systemic toxicity, and improve drug accumulation at the tumor site via the EPR effect. Furthermore, by functionalizing the liposomal surface with targeting ligands like antibodies or peptides, the specificity of drug delivery to cancer cells can be significantly increased, thereby enhancing the therapeutic efficacy and reducing side effects [121,122]. Polymeric nanoparticles can be designed to deliver a wide range of chemotherapeutic agents in a controlled release manner, improving the treatment of various cancers. Moreover, the surface of these nanoparticles can be modified with tumor-targeting ligands, such as folate, transferrin, or HER2- specific antibodies, enabling them to selectively bind to and enter tumor cells. These nanoparticles can also be used for combination therapy, where multiple drugs with complementary mechanisms of action are co-delivered, improving the overall therapeutic outcome [123,124]. Magnetic nanoparticles (MNPs), especially superparamagnetic iron oxide nanoparticles (SPIONs), are also gaining attention in cancer therapy due to their ability to be guided by an external magnetic field, allowing for localized drug delivery and tumor targeting. SPIONs can be loaded with chemotherapeutic agents, and their release can be controlled via the application of a magnetic field. Moreover, MNPs can be used for hyperthermia therapy, where an alternating magnetic field induces localized heating of the nanoparticles, resulting in the destruction of tumor cells [125,126].

Nanoparticles in Vaccine Development
Nanoparticles have emerged as valuable tools in the development of vaccines, offering numerous advantages over traditional vaccine delivery systems. Their ability to encapsulate antigens, protect them from degradation, and present them to the immune system in a controlled manner has made nanoparticles an attractive platform for vaccine development. Liposomes, polymeric nanoparticles, and protein nanoparticles have been extensively studied for use in both prophylactic and therapeutic vaccines.

Nanoparticles can serve as adjuvants in vaccines, enhancing the immune response by stimulating both the innate and adaptive immune systems. Nanoparticle-based vaccines are particularly effective at targeting antigen-presenting cells (APCs), such as dendritic cells, and facilitating the uptake and processing of the antigens. The surface of nanoparticles can be functionalized with specific ligands to enhance targeting to APCs and improve vaccine efficacy. Nanoparticles also enable the development of needle- free vaccines, as they can be administered through alternative routes, such as intranasal or transdermal delivery, reducing the need for injections [127,128]. The success of mRNA vaccines, such as the Pfizer-Bion Tech and Modern a COVID-19 vaccines, has highlighted the importance of lipid nanoparticles (LNPs) in vaccine development. LNPs efficiently deliver the mRNA to cells, where it is translated into the antigen to stimulate an immune response. These nanoparticles have proven to be highly effective in providing immunity against infectious diseases and are expected to play a critical role in the development of vaccines for other diseases, including cancer and HIV [129,130].

Future Directions and Conclusion

The field of nanoparticle-based pharmaceutical applications has witnessed significant advancements over the past few decades, opening new avenues for the treatment and prevention of diseases. However, despite the promising potential, several challenges remain, and much remains to be explored in terms of their clinical translation, safety, and regulatory approval. As the field continues to evolve, a number of future directions stand out that can potentially transform pharmaceutical and medical practices.
 
 Future Directions
One of the key future directions in the development of nanoparticles for pharmaceutical applications is the personalization of drug delivery. Personalized medicine aims to tailor medical treatment to individual characteristics of each patient, including their genetic makeup, lifestyle, and specific disease conditions. Nanoparticles can play a critical role in this field by enabling precise targeting of therapeutic agents, reducing side effects, and enhancing drug efficacy. By combining nanoparticles with biomarkers or genetically tailored therapies, it is possible to create more individualized treatment regimens, particularly for complex diseases like cancer, cardiovascular disorders, and autoimmune diseases. Personalized nanomedicine could also improve the outcomes of gene therapies, allowing for specific targeting of gene-editing tools to the patient's unique genetic profile, potentially enhancing therapeutic efficiency and minimizing adverse effects [131,132].

Another important area of future research is the scalability and cost-effectiveness of nanoparticle production. While the laboratory-scale synthesis of nanoparticles is relatively well- established, the transition to large-scale production remains a significant hurdle. For nanoparticles to achieve widespread clinical and commercial adoption, scalable manufacturing methods must be developed that are reproducible, cost-efficient, and able to meet regulatory standards. Technologies like microfluidics, 3D printing, and continuous flow reactors are being explored to overcome these challenges. Moreover, efforts to simplify the synthesis of nanoparticles and reduce the use of expensive reagents can make nanomedicines more affordable and accessible to a broader patient population, particularly in low-resource settings [133,134].

The biocompatibility and safety of nanoparticles are among the most pressing concerns that need to be addressed to facilitate their clinical translation. Although many nanoparticles, such as liposomes and polymeric nanoparticles, have demonstrated biocompatibility in preclinical studies, issues related to their long- term toxicity, immune responses, and clearance from the body remain largely unexplored. There is an urgent need for systematic, long-term studies to evaluate the biodistribution, metabolism, and excretion of nanoparticles to ensure their safety in clinical applications. Moreover, the development of nanoparticles with biodegradable and bioresorbable properties, which would eliminate the risk of accumulation in tissues, is a critical goal for future research [135,136]. Furthermore, the development of multifunctional nanoparticles is an exciting frontier in the field of pharmaceutical nanotechnology. Multifunctional nanoparticles are designed to perform multiple tasks simultaneously, such as carrying and releasing therapeutic drugs, imaging agents, and targeting ligands. By combining these capabilities into a single nanoparticle platform, it is possible to create nanoparticles that can both diagnose and treat diseases in a single step, a concept referred to as theranostics. For example, nanoparticles can be engineered to carry chemotherapy drugs while simultaneously delivering imaging agents to monitor the drug’s distribution in real time.
 
This integration of diagnostics and therapeutics could significantly improve the management of complex diseases, such as cancer, by enabling real-time monitoring of treatment efficacy and reducing the need for invasive procedures [137,138]. In the area of cancer nanotherapy, the future direction of research is heavily focused on overcoming the challenges associated with tumor heterogeneity and the blood-brain barrier (BBB). Tumors are often composed of heterogeneous cell populations that exhibit varying degrees of resistance to treatment. To address this, researchers are exploring the use of nanoparticles that can simultaneously deliver multiple therapeutic agents or employ combinatory therapies to overcome resistance. Moreover, delivering drugs to tumors within the brain remains a major challenge due to the restrictive nature of the BBB. Nanoparticles, particularly those that are functionalized with specific ligands, hold great promise in overcoming this barrier and delivering drugs, gene therapies, or imaging agents directly to brain tumors, as well as other challenging sites [139].

Another crucial area of future investigation is the clinical translation of RNA-based therapies using lipid nanoparticles (LNPs). The success of the COVID-19 mRNA vaccines has demonstrated the incredible potential of LNPs for RNA delivery. The future of RNA-based therapies is likely to expand beyond vaccines and into treatments for genetic disorders, cancer, and other conditions. Research is currently focused on enhancing the efficiency of LNPs in delivering RNA to the target cells, as well as improving their stability, shelf life, and targeting specificity. Furthermore, exploring the use of LNPs in combination with other therapies, such as immunotherapies or gene editing technologies, may lead to synergistic effects and more effective treatments. The development of nanoparticle based vaccines also holds great promise for the future. Nanoparticles, particularly LNPs and virus like particles (VLPs), are being extensively explored as platforms for the delivery of antigens in both prophylactic and therapeutic vaccines. The flexibility of nanoparticles in encapsulating a wide range of antigens, coupled with their ability to modulate immune responses, makes them excellent candidates for addressing complex infectious diseases, such as HIV, malaria, and tuberculosis, as well as cancers. Additionally, nanoparticle vaccines have the potential to be administered via alternative routes such as oral, nasal, or transdermal, which could improve patient compliance and ease of distribution. The success of mRNA vaccines for COVID-19 has accelerated interest in this area, and it is anticipated that future vaccines will continue to leverage nanoparticle technology for greater effectiveness and broader application.
 

Conclusion

Nanoparticles have proven to be an invaluable tool in pharmaceu- tical science, with their applications spanning drug delivery, diag- nostics, gene therapy, cancer treatment, and vaccine development. Their unique properties, such as small size, high surface area, and the ability to be functionalized, allow them to carry a variety of therapeutic agents and target specific tissues or cells with high precision. As the field continues to evolve, the future of nanopar- ticle-based therapies is promising, with numerous advancements expected in areas such as personalized medicine, multifunctional nanoparticles, and RNA-based therapies. However, several chal- lenges remain, particularly concerning the safety, scalability, and regulatory approval of these nanomedicines. Addressing these challenges through innovative research and technological ad- vancements will pave the way for the broader adoption of nanopar- ticles in clinical practice. The continued development of nanopar- ticles holds great potential to revolutionize the treatment of a wide range of diseases, providing safer, more effective, and more target- ed therapeutic options for patients worldwide. Nanoparticles are poised to play a critical role in the future of medicine. With the ongoing exploration of new nanoparticle types, improved manu- facturing techniques, and a deeper understanding of their interac- tions within the body, we are on the cusp of a new era in pharma- ceutical innovation. By overcoming the current barriers to clinical translation and ensuring their safety and efficacy, nanoparticles can significantly improve the treatment and prevention of diseases, ul- timately leading to more personalized and efficient healthcare.

References

1.    Thakur, R. S., & Agrawal, R. (2015). Application of nano- technology in pharmaceutical formulation design and devel- opment. Current Drug Therapy, 10(1), 20–34.

2.    Kumar, C. S. S. R. (2010). Nanotechnology tools in pharma- ceutical R&D. Materials Today, 12(Suppl.), 24–30.

3.    Patil, M. P., & Nemade, L. S. (2023). Nanoarchitectured Ma- terials: Their Applications and Present Scenarios in Drug De- livery. Advances in Novel Formulations for Drug Delivery, 1-27.

4.    Demetzos, C., Kavatzikidou, P., Pippa, N., & Stratakis, E. (2020). Nanomedicines and nanosimilars: looking for a new and dynamic regulatory “Astrolabe” inspired system. AAPS PharmSciTech, 21, 1-9.

5.    McNeil, S. E. (2011). Unique benefits of nanotechnology to drug delivery and diagnostics. Characterization of nanoparti- cles intended for drug delivery, 3-8.

6.    Croitoru, G. A., Pîrvulescu, D. C., Niculescu, A. G., Grumez- escu, A. M., Antohi, A. M., & Nicolae, C. L. (2024). Metal- lic nanomaterials–targeted drug delivery approaches for im- proved bioavailability, reduced side toxicity, and enhanced patient outcomes. Romanian Journal of Morphology and Em- bryology, 65(2), 145.

7.    Borthakur, P. P., Sarmah, P., Das, D., & Saikia, M. (2023). Nanotechnology: Exploring its applications in mechanical en- gineering. Modern Trends in Mechanical Engineering, 1(1), 31–55.

8.    Pathak, K., Ahmad, M. Z., Saikia, R., Borthakur, P. P., Pra- manik, P., Islam, M. A., ... & Gogoi, S. (2024). Nanohybrid cerasomes: Advancements in targeted drug and gene delivery. European Journal of Medicinal Chemistry Reports, 100178.

9.    Das, A., Saikia, R., Pathak, K., Gogoi, U., & Pathak, M. P. (2020). Anti-diabetic nano-formulation from herbal source. Nano Medicine and Nano Safety: Recent Trends and Clinical Evidences, 61-84.

10.    Pathak, K., & Zaman, K. (2013). Comparetive Pharmacolog- ical Evaluation on The Leaf and Stem Bark of Annona Retic- ulata L. for Antidiabetic Activity. The Pharma Review, 1(3), 65-69.

11.    Pathak, K., & Das, A. (2018). Assessment of antioxidant ac- tivity of different extracts of Annona. International Journal of Pharmaceutical Sciences and Research, 9(6), 2431–2437.

12.    Pathak, K., Das, R. J., Saikia, R., Das, A., & Ahmad, M. Z. (2021). Bora Rice: Natural polymer for drug delivery. Materi- als Proceedings, 7(1), 2.

13.    Saikia, R., Pathak, K., Das, A., & Ahmad, M. Z. (2022, Feb- ruary). The promising shadow of nanohybrid liposomal cera- somes towards the treatment of diabetes mellitus. In Medical Sciences Forum (Vol. 10, No. 1, p. 5). MDPI.

14.    Ahmad, M. Z., Ahmad, J., Alasmary, M. Y., Akhter, S., Aslam, M., Pathak, K., ... & Abdullah, M. M. (2022). Nanoemulgel as an approach to improve the biopharmaceutical performance of lipophilic drugs: Contemporary research and applica- tion. Journal of Drug Delivery Science and Technology, 72, 103420.

15.    Pathak, K., Gogoi, U., Saikia, R., Pathak, M. P., & Das, A. (2022). Marine-derived antidiabetic compounds: an insight into their sources, chemistry, SAR, and molecular mecha- nisms. Studies in Natural Products Chemistry, 73, 467-504.

16.    Ahmad, M. Z., Mohammed, A. A., Pathak, K., Gogoi, U., Saikia, R., & Ahmad, J. (2022). Metallic nanomaterials for the diagnosis and treatment of infectious diseases. In Nanoth- eranostics for Treatment and Diagnosis of Infectious Diseases (pp. 289-317). Academic Press.

17.    Ahmad, M. Z., Alasiri, A. S., Alasmary, M. Y., Abdullah, M. M., Ahmad, J., Abdel Wahab, B. A., ... & Gogoi, U. (2022). Emerging advances in nanomedicine for breast cancer immu- notherapy: Opportunities and challenges. Immunotherapy, 14(12), 957-983.

18.    Ahmad, M. Z., Bhatnagar, D., Ladhe, S., Kumar, D., Pathak, K., Das, R. J., ... & Mustafa, G. (2022). Liposomes and nio- somes for targeted drug and gene delivery systems. In Phar- maceutical Nanobiotechnology for Targeted Therapy (pp. 337-359). Cham: Springer International Publishing.

19.    Saikia, R., Das, A., Pathak, K., Gogoi, N., Paul, T., Sahari- ah, J. J., & Sarma, H. (2022). In Silico Design, Synthesis and Evaluation of Hydroxyxanthone Derivatives as Potential An- ti-diabetic Agents Targeting α-glucosidase. Current Enzyme Inhibition, 18(3), 211-225.

20.    Abdel-Wahab, B. A., Haque, A., Alotaibi, H. F., Alasiri, A. S., Elnoubi, O. A., Ahmad, M. Z., ... & Wahab, S. (2024). Eco-friendly green synthesis of silver nanoparticles utilizing olive oil waste by-product and their incorporation into a chi- tosan-aloe vera gel composite for enhanced wound healing in acid burn injuries. Inorganic Chemistry Communications, 165, 112587.

21.    Naveen, J., Saikia, M., Borah, N., Pathak, K., & Das, R. (2020). Yield performance of organic baby corn (Zea mays L.) as influenced by nutrient management and moisture conserva- tion practices in sandy loam soils of Assam. Indian Journal of Agricultural Research, 54(2), 256-259.

22.    Sonowal, S., Pathak, K., Das, D., Buragohain, K., Gogoi, A., Borah, N., ... & Nath, R. (2024). lâ?Asparaginase Bioâ?Betters: Insight Into Current Formulations, Optimization Strategies and Future Bioengineering Frontiers in Antiâ?Cancer Drug De- velopment. Advanced Therapeutics, 7(10), 2400156.

23.    Das, R. J., Pathak, K., Kalita, P., & Das, P. (2024). Nano-drug delivery systems for the enhancement of bioavailability and bioactivity. In Futuristic Trends in Pharmacy & Nursing, 3 Book 3.

24.    Kalita, P., Jesudasan, R., & Maut, C. (2024). Advancements in antidiabetic therapy: An extensive study on the use of polyp- ills to treat type 2 diabetes. Bioequivalence & Bioavailability International Journal.

25.    Bora, A., Kalita, P., Kalita, P., Adhikari, R. P., Das, A., Zaheer, R., ... & Pathak, K. (2025). Harnessing the Therapeutic Poten- tial of Dillenia indica: An Overview of Recent Dosage Form Developments. Current Drug Discovery Technologies, 22(1), E170424229033.

26.    Dobrovolskaia, M. A. (2022). Lessons learned from immuno- logical characterization of nanomaterials at the Nanotechnol- ogy Characterization Laboratory. Frontiers in Immunology, 13, 984252.

27.    Chen, S., Zhang, Q., Hou, Y., Zhang, J., & Liang, X. J. (2013). Nanomaterials in medicine and pharmaceuticals: nanoscale materials developed with less toxicity and more efficacy. Eu- ropean Journal of Nanomedicine, 5(2), 61-79.

28.    Hurst, S. J. (2011). Biomedical nanotechnology. In Methods in Molecular Biology, 726, 1–13.

29.    Nadendla, R. R., & Chandu, U. M. (2024). Future trends in pharmaceutical sciences: Nanosynth and the evolution of drug delivery through nanoparticle synthesis. Pharma Times, 56(8), 25–29.

30.    Egbuna, C., GÃÂ??man, M.-A., & Jeevanandam, J. (2022). Appli- cations of nanotechnology in drug discovery and delivery. In Applications of Nanotechnology in Drug Discovery and De- livery, 1–429.

31.    Bhowmick, T. K., Gayen, K., & Maity, S. K. (2024). Nano- biotechnology: Applications of nanomaterials in biotechnol- ogy, medicine, and healthcare. In Nanobiotechnology: Appli- cations of Nanomaterials in Biotechnology, Medicine, and Healthcare, 1–344.

32.    Martins, L. H. S., Rai, M., Neto, J. M., de Oliveira, J. A. R., Martins, J. H. S., Komesu, A., Moreira, D. K. T., & Gomes, P. W. P. (2017). Nanomaterials: Properties, toxicity, safety, and drug delivery. In Nanotechnology Applied to Pharmaceutical Technology, 363–381.

33.    El-Hack, M. E. A., Alagawany, M., Farag, M. R., Arif, M., Emam, M., Dhama, K., Sarwar, M., & Sayab, M. (2017). Nu- tritional and pharmaceutical applications of nanotechnology: Trends and advances. International Journal of Pharmacology, 13(4), 340–350.

34.    Dey, S., Mazumder, B., & Pathak, Y. (2014). Models for risk assessments of nanoparticles. In Biointeractions of Nanoma- terials, 383–423.

35.    Grognet, J. M. (2008). Nanotechnologies: from information sciences to pharmacology. Therapie, 63(1), 1-9.

36.    Abbott, L. C., & Maynard, A. D. (2010). Exposure assessment approaches for engineered nanomaterials. Risk Analysis: An International Journal, 30(11), 1634-1644. 

37.    Abdelhalim, M. A. K. (2011). Gold nanoparticles administra- tion induces disarray of heart muscle, hemorrhagic, chronic inflammatory cells infiltrated by small lymphocytes, cytoplas- mic vacuolization and congested and dilated blood vessels. Lipids in health and disease, 10, 1-9.

38.    Anjum, N. A., Adam, V., Kizek, R., Duarte, A. C., Pereira, E., Iqbal, M., ... & Ahmad, I. (2015). Nanoscale copper in the soil–plant system–toxicity and underlying potential mecha- nisms. Environmental Research, 138, 306-325.

39.    Anjum, N. A., Rodrigo, M. A. M., Moulick, A., Heger, Z., Ko- pel, P., Zítka, O., ... & Kizek, R. (2016). Transport phenomena of nanoparticles in plants and animals/humans. Environmen- tal Research, 151, 233-243.

40.    AshaRani, P. V., Low Kah Mun, G., Hande, M. P., & Vali- yaveettil, S. (2009). Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS nano, 3(2), 279-290.

41.    Asharani, P. V., Wu, Y. L., Gong, Z., & Valiyaveettil, S. (2008). Toxicity of silver nanoparticles in zebrafish models. Nanotechnology, 19(25), 255102.

42.    Bahadar, H., Maqbool, F., Niaz, K., & Abdollahi, M. (2016). Toxicity of nanoparticles and an overview of current experi- mental models. Iranian biomedical journal, 20(1), 1.

43.    Basu, R., Harris, M., Sie, L., Malig, B., Broadwin, R., & Green, R. (2014). Effects of fine particulate matter and its constituents on low birth weight among full-term infants in California. Environmental Research, 128, 42-51.

44.    Bondi, M. L., Montana, G., Craparo, E. F., Picone, P., Capua- no, G., Carlo, M. D., & Giammona, G. (2009). Ferulic ac- id-loaded lipid nanostructures as drug delivery systems for Alzheimer's disease: Preparation, characterization and cyto- toxicity studies. Current Nanoscience, 5(1), 26-32.

45.    Cattaneo, A. G., Gornati, R., Sabbioni, E., Chirivaâ?Internati, M., Cobos, E., Jenkins, M. R., & Bernardini, G. (2010). Nan- otechnology and human health: risks and benefits. Journal of applied Toxicology, 30(8), 730-744.

46.    Chupani, L., Zusková, E., Niksirat, H., PanáÃÂ?ek, A., Lüns- mann, V., Haange, S. B., ... & Jehmlich, N. (2017). Effects of chronic dietary exposure of zinc oxide nanoparticles on the serum protein profile of juvenile common carp (Cyprinus carpio L.). Science of the total environment, 579, 1504-1511.

47.    Daraee, H., Eatemadi, A., Abbasi, E., Fekri Aval, S., Kouhi, M., & Akbarzadeh, A. (2016). Application of gold nanopar- ticles in biomedical and drug delivery. Artificial cells, nano- medicine, and biotechnology, 44(1), 410-422.

48.    Abbott, L. C., & Maynard, A. D. (2010). Exposure assessment approaches for engineered nanomaterials. Risk Analysis: An International Journal, 30(11), 1634-1644.

49.    Abdelhalim, M. A. K. (2011). Gold nanoparticles administra- tion induces disarray of heart muscle, hemorrhagic, chronic inflammatory cells infiltrated by small lymphocytes, cytoplas- mic vacuolization and congested and dilated blood vessels. Lipids in health and disease, 10, 1-9.

50.    Anjum, N. A., Adam, V., Kizek, R., Duarte, A. C., Pereira, E., Iqbal, M., ... & Ahmad, I. (2015). Nanoscale copper in the soil–plant system–toxicity and underlying potential mecha- nisms. Environmental Research, 138, 306-325. 

51.    Anjum, N. A., Rodrigo, M. A. M., Moulick, A., Heger, Z., Ko- pel, P., Zítka, O., ... & Kizek, R. (2016). Transport phenomena of nanoparticles in plants and animals/humans. Environmen- tal Research, 151, 233-243.

52.    AshaRani, P. V., Low Kah Mun, G., Hande, M. P., & Vali- yaveettil, S. (2009). Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS nano, 3(2), 279-290.

53.    Asharani, P. V., Wu, Y. L., Gong, Z., & Valiyaveettil, S. (2008). Toxicity of silver nanoparticles in zebrafish models. Nanotechnology, 19(25), 255102.

54.    Bahadar, H., Maqbool, F., Niaz, K., & Abdollahi, M. (2016). Toxicity of nanoparticles and an overview of current experi- mental models. Iranian biomedical journal, 20(1), 1.

55.    Basu, R., Harris, M., Sie, L., Malig, B., Broadwin, R., & Green, R. (2014). Effects of fine particulate matter and its constituents on low birth weight among full-term infants in California. Environmental Research, 128, 42-51.

56.    Bondi, M. L., Montana, G., Craparo, E. F., Picone, P., Capua- no, G., Carlo, M. D., & Giammona, G. (2009). Ferulic ac- id-loaded lipid nanostructures as drug delivery systems for Alzheimer's disease: Preparation, characterization and cyto- toxicity studies. Current Nanoscience, 5(1), 26-32.

57.    Cattaneo, A. G., Gornati, R., Sabbioni, E., Chirivaâ?Internati, M., Cobos, E., Jenkins, M. R., & Bernardini, G. (2010). Nan- otechnology and human health: risks and benefits. Journal of applied Toxicology, 30(8), 730-744.

58.    Borthakur, B., & Borthakur, P. P. (2024). The role of thermal analysis in engine fin design: Insights and perspectives. Re- cent Patents on Engineering, 18(8), 153-161.

59.    Chupani, L., Zusková, E., Niksirat, H., PanáÃÂ?ek, A., Lüns- mann, V., Haange, S. B., ... & Jehmlich, N. (2017). Effects of chronic dietary exposure of zinc oxide nanoparticles on the serum protein profile of juvenile common carp (Cyprinus carpio L.). Science of the total environment, 579, 1504-1511.

60.    Daraee, H., Eatemadi, A., Abbasi, E., Fekri Aval, S., Kouhi, M., & Akbarzadeh, A. (2016). Application of gold nanopar- ticles in biomedical and drug delivery. Artificial cells, nano- medicine, and biotechnology, 44(1), 410-422.

61.    Akbarzadeh, A., Rezaei-Sadabady, R., Davaran, S., Joo, S. W., Zarghami, N., Hanifehpour, Y., ... & Nejati-Koshki, K. (2013). Liposome: classification, preparation, and applica- tions. Nanoscale research letters, 8, 1-9.

62.    Rahman, A., Carmichael, D., Harris, M., & Roh, J. K. (1986). Comparative pharmacokinetics of free doxorubicin and doxo- rubicin entrapped in cardiolipin liposomes. Cancer research, 46(5), 2295-2299.

63.    Davis, D., Davies, A., & Gregoriadis, G. (1986). Liposomes as immunological adjuvants in vaccines: Studies with entrapped and surface-linked antigen. Biochemical Society Transac- tions, 14(6), 1036-1037.

64.    Minchinton, A. I., & Tannock, I. F. (2006). Drug penetration in solid tumours. Nature Reviews Cancer, 6(8), 583-592.

65.    Allen, T. M. (1998). Liposomal drug formulations: rationale for development and what we can expect for the future. Drugs, 56(5), 747-756.

66.    Drummond, D. C., Meyer, O., Hong, K., Kirpotin, D. B., & Papahadjopoulos, D. (1999). Optimizing liposomes for deliv- ery of chemotherapeutic agents to solid tumors. Pharmaco- logical reviews, 51(4), 691-743.

67.    Allen, T. M., & Cullis, P. R. (2004). Drug delivery systems: entering the mainstream. Science, 303(5665), 1818-1822.

68.    Hobbs, S. K., Monsky, W. L., Yuan, F., Roberts, W. G., Grif- fith, L., Torchilin, V. P., & Jain, R. K. (1998). Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proceedings of the National Academy of Sciences, 95(8), 4607-4612.

69.    Yuan, F., Leunig, M., Huang, S. K., Berk, D. A., Papahad- jopoulos, D., & Jain, R. K. (1994). Mirovascular permeabili- ty and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft. Cancer research, 54(13), 3352-3356.

70.    Yatvin, M. B., Weinstein, J. N., Dennis, W. H., & Blumenthal, R. (1978). Design of liposomes for enhanced local release of drugs by hyperthermia. Science, 202(4374), 1290-1293.

71.    Kong, G., Anyarambhatla, G., Petros, W. P., Braun, R. D., Colvin, O. M., Needham, D., & Dewhirst, M. W. (2000). Ef- ficacy of liposomes and hyperthermia in a human tumor xe- nograft model: importance of triggered drug release. Cancer research, 60(24), 6950-6957.

72.    Yarmolenko, P. S., Zhao, Y., Landon, C., Spasojevic, I., Yuan, F., Needham, D., ... & Dewhirst, M. W. (2010). Comparative effects of thermosensitive doxorubicin-containing liposomes and hyperthermia in human and murine tumours. Internation- al Journal of Hyperthermia, 26(5), 485-498.

73.    Kono, K., Yoshino, K., & Takagishi, T. (2002). Effect of poly (ethylene glycol) grafts on temperature-sensitivity of thermo- sensitive polymer-modified liposomes. Journal of Controlled Release, 80(1-3), 321-332.

74.    Kulkarni, P. R., Yadav, J. D., & Vaidya, K. A. (2011). Lipo- somes: A novel drug delivery system. International Journal of Current Pharmaceutical Research, 3(2), 10-18.

75.    Padmanabhan, R. V., Gudapaty, R., Liener, I. E., Schwartz,

B. A., & Hoidal, J. R. (1985). Protection against pulmonary oxygen toxicity in rats by the intratracheal administration of liposome-encapsulated superoxide dismutase or catalase. American Review of Respiratory Disease, 132(1), 164-167.

76.    Forssen, E. A., & Ross, M. E. (1994). Daunoxome® treatment of solid tumors: preclinical and clinical investigations. Jour- nal of liposome research, 4(1), 481-512.

77.    Fricker, G., Kromp, T., Wendel, A., Blume, A., Zirkel, J., Reb- mann, H., ... & Müller-Goymann, C. (2010). Phospholipids and lipid-based formulations in oral drug delivery. Pharma- ceutical research, 27(8), 1469-1486.

78.    Gregoriadis, G., & Florence, A. T. (1993). Liposomes in drug delivery: clinical, diagnostic and ophthalmic potential. Drugs, 45, 15-28.

79.    Lasic, D. D., & Papahadjopoulos, D. (1998). Medical applica- tions of liposomes.

80.    Patel, G. B., Agnew, B. J., Deschatelets, L., Fleming, L. P., & Sprott, G. D. (2000). In vitro assessment of archaeosome stability for developing oral delivery systems. International journal of pharmaceutics, 194(1), 39-49. 

81.    Sprott, G. D. (1992). Structures of archaebacterial membrane lipids. Journal of Bioenergetics and Biomembranes, 24, 555- 566.

82.    Woodle, M. C., & Lasic, D. D. (1992). Sterically stabilized liposomes. BBA - Reviews on Biomembranes, 1113(2), 171- 199.

83.    Wörner, C., & Mülhaupt, R. (1993). Polynitrileâ?and polyam- ineâ?functional poly (trimethylene imine) dendrimers. Ange- wandte Chemie International Edition in English, 32(9), 1306- 1308.

84.    Blume, G., & Cevc, G. (1993). Molecular mechanism of the lipid vesicle longevity in vivo. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1146(2), 157-168.

85.    Samad, A., Sultana, Y., & Aqil, M. (2007). Liposomal drug delivery systems: an update review. Current drug delivery, 4(4), 297-305.

86.    Biju, S., Talegaonkar, S., Mishra, P., & Khar, R. (2006). Vesic- ular systems: An overview. Indian Journal of Pharmaceutical Sciences, 68(2), 141-153.

87.    Bhatt, D. A., & Pethe, A. M. (2010). Nanotechnology: A promising drug delivery system. International Journal of Pharm Tech Research, 2(2), 1331-1345.

88.    Dev, A., & Mehra, N. K. (2007). Liposomes: Applications in pharmacology. Indian Journal of Pharmaceutical Sciences, 69(3), 303-306. Pathak, K., Saikia, R., & Das, A. (2023). Un-locking the therapeutic potential of Garcinia cowa Rox. in di- abetes management. Sciences of Phytochemistry, 2(1), 38-41.

89.    Pathak, K., Saikia, R., Sarma, H., Pathak, M. P., Das, R. J., Gogoi, U., ... & Wahab, B. A. A. (2023). Nanotheranostics: application of nanosensors in diabetes management. Journal of Diabetes & Metabolic Disorders, 22(1), 119-133.

90.    Pathak, K., Das, R. J., & Baishya, K. (2013). Recent advance- ment of lipid drug conjugate as nanoparticulate drug delivery system. International Research Journal of Pharmacy, 4(1).

91.    Ahmad, M. Z., Ahmad, J., Umar, A., Abdel-Wahab, B. A., La-

hiq, A. A., Khan, Z. N., ... & Munir, S. (2023). Nanomaterials in cancer immunotherapy: A spotlight on breast cancer. Sci- ence of Advanced Materials, 15(3), 285-318.

92.    Das, M. K., & Pathak, Y. V. (2020). Nano medicine and nano safety. Recent Trends an d Clinical Evidences.

93.    Soliman, K. F., & Pathak, Y. V. (Eds.). (2023). Flavonoids and Anti-Aging: The Role of Transcription Factor Nuclear Eryth- roid 2-Related Factor2. CRC Press.

94.    Ahmad, M. Z., Pathak, K., Bhatnagar, D., Ladhe, S., Kumar, D., Saikia, R., & Das, A. (2023). Nanotheranostic Approach for Cancer Treatment. In Handbook of Cancer and Immunolo- gy (pp. 1-32). Cham: Springer International Publishing.

95.    Ahmad, M. Z., Saeed, A. M., Elnoubi, O. A., Alasiri, A. S., Abdel-Wahab, B. A., Alqahtani, A. A., ... & Das, A. (2024). Chitosan-based topical formulation integrated with green-syn- thesized silver nanoparticles utilizing Camellia sinensis leaf extracts: A promising approach for managing infected wounds. International Journal of Biological Macromolecules, 257, 128573.

96.    Pathak, K. (2023). Herbal nanotechnology: innovations and applications in modern medicine. Indian J Nat Products, 14(10), 1-10.

97.    Pathak, K., Ahmad, M. Z., Saikia, R., Pathak, M. P., Jyoti, J., Sahariah, ... & Abdel-Wahab, B. A. (2025). Nanomedicine: A New Frontier in Alzheimer’s Disease Drug Targeting. Central Nervous System Agents in Medicinal Chemistry, 25(1), 3-19.

98.    Kim, S., Kwon, K., Kwon, I. C., & Park, K. (2009). Nanotech- nology in drug delivery: Past, present, and future. Nanotech- nology in drug delivery, 581-596.

99.    Sahoo, S. K., & Labhasetwar, V. (2003). Nanotech approaches to drug delivery and imaging. Drug discovery today, 8(24), 1112-1120.

100.    Hughes, G. A. (2005). Nanostructure-mediated drug delivery. Nanomedicine: nanotechnology, biology and medicine, 1(1), 22-30.

101.    Gupta, A., Arora, A., Menakshi, A., Sehgal, A., & Sehgal, R. (2012). Nanotechnology and its applications in drug delivery: A review. Webmed Central: International Journal of Medical and Molecular Medicine, 3(1), 1-9.

102.    Krishna, K. B., & Prabhakar, C. (2011). A review on nanosus- pensions in drug delivery. International Journal of Pharma and Bio Sciences, 2(1), 549-558.

103.    Pandya, V. M., Patel, J. K., & Patel, D. J. (2011). Formulation, optimization and characterization of simvastatin nanosuspen- sion prepared by nanoprecipitation technique. Der Pharmacia Lettre, 3(2), 129-140.

104.    Thakkar, H. P., Patel, B. V., & Thakkar, S. P. (2011). Develop- ment and characterization of nanosuspensions of olmesartan medoxomil for bioavailability enhancement. Journal of Phar- macy and Bioallied Sciences, 3(3), 426-434.

105.    Borhade, V., Pathak, S., Sharma, S., & Patravale, V. (2014). Formulation and characterization of atovaquone nanosuspen- sion for improved oral delivery in the treatment of malaria. Nanomedicine, 9(5), 649-666.

106.    Chiang, P. C., Ran, Y., Chou, K. J., Cui, Y., & Wong, H. (2011). Investigation of utilization of nanosuspension formu- lation to enhance exposure of 1, 3-dicyclohexylurea in rats: preparation for PK/PD study via subcutaneous route of nano- suspension drug delivery. Nanoscale research letters, 6, 1-9.

107.    Padua, G. W., & Wang, Q. (2012). Nanotechnology research methods for food and bioproducts. John Wiley & Sons.

108.    Uprit, S., Sahu, R. K., Roy, A., & Pare, A. (2013). Preparation and characterization of minoxidil loaded nanostructured lipid carrier gel for effective treatment of alopecia. Saudi Pharma- ceutical Journal, 21(4), 379-385.

109.    Bielinska, A. U., Janczak, K. W., Landers, J. J., Makidon, P., Sower, L. E., Peterson, J. W., & Baker Jr, J. R. (2007). Muco- sal immunization with a novel nanoemulsion-based recombi- nant anthrax protective antigen vaccine protects against Bacil- lus anthracis spore challenge. Infection and immunity, 75(8), 4020-4029.

110.    Azeem, A., Ahmad, F. J., Khar, R. K., & Talegaonkar, S. (2009). Nanocarrier for the transdermal delivery of an anti- parkinsonian drug. AAPS PharmSciTech, 10, 1093-1103.

111.    Tiwari, S. B., & Amiji, M. M. (2006). Improved oral delivery of paclitaxel following administration in nanoemulsion for- mulations. Journal of nanoscience and nanotechnology, 6(9-10), 3215-3221.

112.    Wagner, V., Dullaart, A., Bock, A. K., & Zweck, A. (2006). The emerging nanomedicine landscape. Nature biotechnolo- gy, 24(10), 1211-1217.

113.    Sahoo, S. K., & Labhasetwar, V. (2003). Nanotech approaches to drug delivery and imaging. Drug discovery today, 8(24), 1112-1120.

114.    Keck, C. M., & Müller, R. H. (2006). Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisa- tion. European journal of pharmaceutics and biopharmaceu- tics, 62(1), 3-16.

115.    Shafiq, S., Shakeel, F., Talegaonkar, S., Ahmad, F. J., Khar, R. K., & Ali, M. (2007). Development and bioavailability assess- ment of ramipril nanoemulsion formulation. European jour- nal of pharmaceutics and biopharmaceutics, 66(2), 227-243.

116.    Mistry, A., Stolnik, S., & Illum, L. (2009). Nanoparticles for direct nose-to-brain delivery of drugs. International journal of pharmaceutics, 379(1), 146-157.

117.    Dokoumetzidis, A., & Macheras, P. (2006). A century of dis- solution research: from Noyes and Whitney to the biopharma- ceutics classification system. International journal of phar- maceutics, 321(1-2), 1-11.

118.    Kentish, S., Wooster, T. J., Ashokkumar, M., Balachandran, S., Mawson, R., & Simons, L. (2008). The use of ultrason- ics for nanoemulsion preparation. Innovative Food Science & Emerging Technologies, 9(2), 170-175.

119.    Hughes, G. A. (2005). Nanostructure-mediated drug delivery. Nanomedicine: nanotechnology, biology and medicine, 1(1), 22-30.

120.    Jenning, V., Schäfer-Korting, M., & Gohla, S. (2000). Vitamin A-loaded solid lipid nanoparticles for topical use: drug release properties. Journal of controlled release, 66(2-3), 115-126.

121.    Fernandez, P., André, V., Rieger, J., & Kühnle, A. (2004). Na- no-emulsion formation by emulsion phase inversion. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 251(1-3), 53-58.

122.    Kakran, M., Sahoo, N. G., Li, L., Judeh, Z., Wang, Y., Chong, K., & Loh, L. (2010). Fabrication of drug nanoparticles by evaporative precipitation of nanosuspension. International journal of pharmaceutics, 383(1-2), 285-292.

123.    Jochmans, D. (2008). Novel HIV-1 reverse transcriptase in- hibitors. Virus research, 134(1-2), 171-185.

124.    Koo, O. M., Rubinstein, I., & Onyuksel, H. (2005). Campto- thecin in sterically stabilized phospholipid micelles: a novel nanomedicine. Nanomedicine: Nanotechnology, Biology and Medicine, 1(1), 77-84.

125.    Guo, Y., Wang, X., Shen, Z., Shu, X., & Sun, R. (2013).

Preparation of cellulose-graft-poly (ÃÂ??-caprolactone) nanomi- celles by homogeneous ROP in ionic liquid. Carbohydrate polymers, 92(1), 77-83.

126.    Salazar, J., Ghanem, A., Müller, R. H., & Möschwitzer, J. P. (2012). Nanocrystals: comparison of the size reduction effec- tiveness of a novel combinative method with conventional top-down approaches. European Journal of Pharmaceutics and Biopharmaceutics, 81(1), 82-90.

127.    Ammar, H. O., Salama, H. A., Ghorab, M., & Mahmoud, A.A.    (2010). Development of dorzolamide hydrochloride in situ gel nanoemulsion for ocular delivery. Drug development and industrial pharmacy, 36(11), 1330-1339.

128.    Huang, C., Tang, Z., Zhou, Y., Zhou, X., Jin, Y., Li, D., ... & Zhou, S. (2012). Magnetic micelles as a potential platform for dual targeted drug delivery in cancer therapy. International journal of pharmaceutics, 429(1-2), 113-122.

129.    Aisha, A. F., Ismail, Z., Abu-Salah, K. M., & Majid, A. M. S.A.    (2012). Solid dispersions of α-mangostin improve its aque- ous solubility through self-assembly of nanomicelles. Journal of Pharmaceutical Sciences, 101(2), 815-825.

130.    Myc, A., Kukowska-Latallo, J. F., Bielinska, A. U., Cao, P., Myc, P. P., Janczak, K., ... & Baker Jr, J. R. (2003). Develop- ment of immune response that protects mice from viral pneu- monitis after a single intranasal immunization with influenza A virus and nanoemulsion. Vaccine, 21(25-26), 3801-3814.

131.    Möschwitzer, J., & Müller, R. H. (2006). New method for the effective production of ultrafine drug nanocrystals. Journal of nanoscience and nanotechnology, 6(9-10), 3145-3153.

132.    Bielinska, A. U., Janczak, K. W., Landers, J. J., Markovitz,

D. M., Montefiori, D. C., & Baker Jr, J. R. (2008). Nasal im- munization with a recombinant HIV gp120 and nanoemulsion adjuvant produces Th1 polarized responses and neutralizing antibodies to primary HIV type 1 isolates. AIDS research and human retroviruses, 24(2), 271-281.

133.    Yang, J. Z., Young, A. L., Chiang, P. C., Thurston, A., & Pretzer, D. K. (2008). Fluticasone and budesonide nanosus- pensions for pulmonary delivery: preparation, characteriza-tion, and pharmacokinetic studies. Journal of pharmaceutical sciences, 97(11), 4869-4878.

134.    Thakkar, H. P., Patel, B. V., & Thakkar, S. P. (2011). Develop- ment and characterization of nanosuspensions of olmesartan medoxomil for bioavailability enhancement. Journal of Phar- macy and Bioallied Sciences, 3(3), 426-434.

135.    Azeem, A., Ahmad, F. J., Khar, R. K., & Talegaonkar, S. (2009). Nanocarrier for the transdermal delivery of an anti- parkinsonian drug. AAPS PharmSciTech, 10, 1093-1103.

136.    Gallarate, M., Chirio, D., Bussano, R., Peira, E., Battaglia, L., Baratta, F., & Trotta, M. (2013). Development of O/W na- noemulsions for ophthalmic administration of timolol. Inter- national journal of pharmaceutics, 440(2), 126-134.

137.    Sun, H., Liu, K., Liu, W., Wang, W., Guo, C., Tang, B., ...& Zeng, H. (2012). Development and characterization of a novel nanoemulsion drug-delivery system for potential appli- cation in oral delivery of protein drugs. International Journal of Nanomedicine, 5529-5543.

138.    AbismaÃÂ?±l, B., Canselier, J. P., Wilhelm, A. M., Delmas, H., & Gourdon, C. (2000). Emulsification processes: on-line study by multiple light scattering measurements. Ultrasonics Sonochemistry, 7(4), 187-192.

139.    Patel, G. V., Patel, V. B., Pathak, A., & Rajput, S. J. (2014). Nanosuspension of efavirenz for improved oral bioavailabili- ty: formulation optimization, in vitro, in situ and in vivo eval- uation. Drug development and industrial pharmacy, 40(1), 80-91.