1. INTRODUCTION:

1.1. Brief overview of transdermal drug delivery systems (TDDS):

Transdermal drug delivery systems (TDDS) are controlled techniques of providing medication to the skin at a predetermined and regulated rate. These systems are composed of adhesive devices that hold medications and have a predetermined surface area, allowing them to release a precise amount of medication onto the surface of undamaged skin at a set rate, ensuring it enters the systemic circulation¹. Transdermal delivery offers significant advantages over injectable and oral methods, enhancing patient compliance and bypassing first-pass metabolism². Furthermore, researchers are investigating new methods for delivering treatments throughout the body, with transdermal drug administration emerging as a potential option that use human skin as a channel for systemic drug delivery³. Transdermal therapy has become a strong alternative to oral therapy for delivering medication. This is because oral therapy necessitates maintaining a precise medication concentration in the body by providing a fixed dose at predetermined intervals. This approach frequently causes oscillations in drug levels, resulting in a peak and trough impact that raises the risk of side effects or treatment failure. Additionally, there is often significant drug loss near the target organ, necessitating close monitoring to prevent the risk of overdosing⁴.

The disadvantages of the oral route can be avoided, and the benefits of intravenous drug infusion, such as avoiding hepatic "first pass” elimination to maintain stable and effective therapeutic drug levels in the body, can be effectively replicated, without the associated risks, through transdermal drug delivery via intact skin^5,6.

Table no. 1: Benefits and Drawbacks of TDDS^7,8,9.

Benefits	Drawbacks
For individuals who are unable to take oral drugs, an alternate method.	Adhesion is likely to change with patch and environmental conditions.
Patients who take their medications less frequently are more compliant.	Not appropriate for high drug dose.
Dose delivery is not impacted by diarrhea or vomiting.	Hypersensitivity reactions and skin irritation may occur.
Avoids high and low drug levels while allowing for longer and multiple day dosing intervals.	Because the patch’s size restricts how much may be administered, the medication molecule must be extremely effective.
It helps to prevent gastrointestinal discomfort by blocking the gastrointestinal tract’s enzymes and first-pass hepatic metabolism.	Adhesion can change with patch type and conditions.
Drug delivery is stopped when the patch is removed.	Different areas of the skin have different barrier function, as well as individuals with varying ages.
Self-administration is feasible, allowing for a continuous and extended release of the drug.	Only little lipophilic medications may currently be administered through the skin with effectiveness.

1.2. Significance of Sustained Release in Transdermal Drug Delivery Systems:

Sustained release systems allow for the slowly release of medication over longer periods, offering control over the timing and location of drug delivery within the body. This means that the system can maintain consistent drug levels in the targeted tissues or cells¹⁰.

Extended release in transdermal drug delivery systems is important for several reasons, particularly because it improves the safety and effectiveness of administering medications.

1.2.1 Advantages of Sustained Release:

1) Patient Compliance: Long-term management of chronic diseases often faces issues with patient compliance, as the effectiveness of drug treatments relies heavily on a patient’s ability to stick to their prescribed regimen. Several factors influence patient compliance, including their understanding of the disease, belief in the treatment, and awareness of the importance of following a strict treatment plan. Adherence may also be impacted by the severity of systemic or local side effects, the expense of medications, and the complexity of treatment plans. However, patient non-compliance can be partly solved with drug delivery systems that release the medication slowly over time^11,14.

2) Uniform Drug Concentration: Sustained release causes the drug to be released at a steady rate over a prolonged period, bringing about a constant concentration within the bloodstream. This minimizes drug level fluctuations, which are known to cause side effects or reduce the effectiveness of the drug¹².

3) Decreased Frequency of Dosing: Through the provision of a steady release of the drug, sustained release products minimize the dosing frequency. This improves patient compliance, especially in chronic illness where compliance with medication regimen is critical^13,14.

4) Lower total dose: Long-acting drug delivery systems are known to utilize a smaller total amount of medication to treat various health conditions. Reduced overall medicine dosage results in a noticeable decrease in both systemic and local adverse effects. This strategy also helps to reduce costs¹⁴.

5) Improved Therapeutic Effectiveness: Sustained release methods can improve drug delivery by allowing drug levels to be sustained throughout time, preventing the agent from becoming ineffective despite regular administration^10,12,14.

6) Reduced Side Effects: The continuous administration of drugs lowers peak and trough effects of traditional dosing schedules, thereby minimizing potential side effects¹⁴.

Briefly, long-term drug release in transdermal delivery systems provides a promising approach to enhance drug efficacy, reduce dosing frequency, minimize side effects, and ultimately improve patient outcomes.

1.3 Introduction to zinc oxide nanoparticles:

Zinc oxide nanoparticles (ZnO NPs) are multifunctional materials with a broad variety of applications due to their characteristics. Zinc oxide is an inorganic chemical substance that is widely used in everyday life. In recent years, the rapid growth of nanotechnology has made it possible to synthesize zinc oxide nanoparticles with unique characteristics¹⁵. ZnO-NPs with diameters less than 100 nm exhibit better catalytic capabilities due to the nanoparticle’s high surface-to-volume ratio^16,17.

ZnO is a conventional semiconductor with a large band-gap. Due to its specific properties, it is suitable for diverse biomedical applications, ranging from anticancer, antibacterial, to antifungal applications¹⁸. The majority of the biomedical applications of ZnO NPs are based on the fact that they are capable of producing ROS, causing cell death if antioxidative potential of the cell is inhibited¹⁹.

2. FUNDAMENTALS OF TRANSDERMAL DRUG DELIVERY:

2.1 Skin structure and permission pathways:

2.1.1 Basic Skin Structure:

The skin consists principally of three layers: the epidermis, dermis, and hypodermis (Fig. 1)^20,21,22,23. The human epidermis normally comprises of roughly 40 to 50 layers of squamous epithelial cells, of which keratinocytes are the most frequent cell type. Typically, the epidermis is divided into four layers: stratum basale, stratum spinosum, stratum granulosum, and stratum corneum. The stratum basale has a basal layer at the bottom, which is formed of progenitor cells, the least differentiated and youngest keratinocytes that replace the epidermis continuously. Human keratinocytes undergoing differentiation may take 30-40 days to move from the basal layer to the skin surface and desquamate²⁴. There are also Merkel cells and melanocytes in the basal layer that synthesize pigment^{25, 26}. When keratinocytes are divided vertically with respect to the basement membrane, they are involved in the production of keratin by differentiation and when horizontally divided, they are concerned with wound healing by proliferation. This layer is differentiated from the dermis by a basement membrane known as the basal lamina. The stratum granulosum and stratum spinosum consist of nucleated keratinocytes. These two layers combine to produce 15 to 20 layers, with the stratum granulosum containing numerous granules that play an important role in keratin synthesis. Langerhans cells are present in all levels of the epidermis, with a larger abundance in the stratum spinosum. As the nucleus and intracellular organelles degrade, keratin deposits to form the stratum corneum. During keratinization, keratin continues to accumulate, creating a flexible yet robust barrier of dead keratinocytes on the skin’s surface. The stratum corneum typically forms a layer of keratinized keratinocytes that is about 10–20µm thick, posing a considerable challenge for molecules applied topically²⁷. The dermis, located beneath the epidermis, is primarily made up of connective tissue that contains fibers such as elastin and collagen²⁸.

In comparison to the large number of keratinocytes required in the epidermis, the fibroblasts responsible for producing these fibers are few. The hypodermis is an adipose tissue-containing region located beneath the dermal layer. This layer, like the dermis, is made up of mesoderm tissues. Thus, mesenchymal stem cells in the fat layer can develop into fibroblasts. Blood vessels are mostly found in the dermis and hypodermis, but they can extend to the epidermis if necessary. Blood vessels are widely distributed in the epidermis in skin-growing areas such as moles, warts, and tumors²⁹. To ensure appropriate efficiency, transdermal administration requires dispersion throughout all skin layers, not just the stratum corneum.

Figure 1: Schematic illustration of the structure of skin

2.1.2. Routes of penetration:

There are three critically important ways a medicinal molecule can penetrate through the intact stratum corneum (SC): Skin appendages (shunt pathways), intercellular lipid areas, or a transcellular route (Fig 2). The physicochemical properties of the molecule determine how effectively a drug can traverse these routes^30,31.

Figure 2: Drug penetration pathways across skin

2.1.2.1 Transappendageal pathway:

Transappendageal channels, also known as shunt routes, involve the absorption of chemicals via hair follicles and associated sebaceous and sweat glands. These skin appendages form a continuous passage through the stratum corneum barrier. Recent research has challenged the long-standing belief that hair follicles make up about 0.1% of the human skin's surface. It turns out that parameters such as follicle count, pore size, and follicular volume are critical for successful medication administration via these appendages. Interestingly, the forehead has roughly 13.7 mm²/cm² of follicular infundibula, which means that about 13.7% of the surface area has follicles. Moreover, the same research confirmed that the widely accepted idea of follicles comprising roughly 0.1% of the stratum corneum is indeed accurate for the skin on the forearm as well^31,32.

2.1.2.2 Transcellular pathway:

Drugs that enter the skin via the transcellular pathway have to travel through the corneocytes. The corneocytes, composed of well-hydrated keratin, create a moist environment that allows hydrophilic drugs to move through. The transcellular pathway includes not only partitioning and diffusion into keratin cells, but also transport into and via the lipids that exist between them^31,33.

2.1.2.3 Intercellular pathway:

The intercellular pathway is where the drug moves through the continuous lipid matrix. This pathway can be difficult for a number of reasons. First, if we consider the “bricks and mortar” model of the stratum corneum, the way corneocytes interdigitate creates a more complex route for the drug to penetrate between cells, as opposed to the straightforward path offered by the transcellular route. Second, the intercellular space consists of alternating bilayer structures. This means that a medicine must gradually partition and pass across a sequence of aqueous and lipid surfaces. This is widely acknowledged as the standard route for most tiny uncharged compounds to enter the skin³³.

2.2 Strategies for promoting drug permeation:

2.2.1 Permeation enhancers:

One traditional method for improving transdermal drug delivery (TDD) is the use of penetration enhancers, also known as sorption promoters or accelerants. These enhancers increase the permeability of the stratum corneum (SC), allowing higher therapeutic concentrations of the drug candidate to be achieved. They function by interacting with the structural elements of the SC, thus altering its barrier properties and enhancing permeability. There are several suggested routes for drug penetration via the skin, including nonpolar, polar, and nonpolar/polar pathways. Penetration enhancers speed up this process by modifying one of these routes. To modify the polar route, the intention is to produce a conformational change in proteins or induce swelling in the solvent. To modify the nonpolar route, effort is focused on changing the rigidity of the lipid structure and fluidizing the crystalline route, which can enhance the velocity of diffusion by nearly double. Fatty acid enhancers boost the fluidity of the lipid component in the stratum corneum (SC). Furthermore, certain enhancers, known as binary carriers, can influence both polar and nonpolar pathways by changing the multilaminate structure through which penetrants move^5,34. The methods for changing the barrier qualities of the stratum corneum (SC) to improve drug penetration and absorption through the skin are divided into two categories: (1) chemical approaches and (2) physical enhancement techniques.

I. Chemical approaches:

Accelerants, absorption promoters, or penetration enhancers are terms used to describe drugs that, when applied topically, aid in improving the absorption of other pharmaceuticals³⁴. Chemical enhancers work in a variety of ways

a) By acting as co-solvents, they improve (and optimize) the drug’s thermodynamic activity.

b) They increase the drug’s partition coefficient, which facilitates its release from the vehicle and skin absorption.

c) The stratum corneum (SC) is prepared to enhance drug diffusion, which facilitates penetration and the development of a drug reservoir inside the SC.

When it comes to skin penetration enhancers, there are several key properties that people really look for:

a. They ought to be safe, gentle on the skin, and free from allergens.

b. Ideally, they should act swiftly and deliver consistent, reliable results.

c. They shouldn’t have any medicinal effects in the body, meaning they shouldn’t attach to receptor sites.

d. Enhancers must enable the introduction of therapeutic drugs into the body while limiting the loss of natural chemicals.

e. They should be able to restore the skin’s barrier function quickly and completely once removed.

f. The enhancers should be compatible with both excipients and drugs and appropriate for a range of topical formulations.

g. They must be cosmetically acceptable and give a comfortable skin feel^1,35.

Some of the most researched permeation enhancers include dimethyl sulfoxide (DMSO), fatty acids like oleic acid, alcohols such as methanol, glycols like propylene glycol, surfactants (specifically anionic surfactants), and azone (lauracapran), among others.

II. Physical enhancement techniques:

Iontophoresis and ultrasound, often known as phonophoresis or sonophoresis, are physical techniques used to improve the penetration and absorption of various medicinal chemicals through the skin^4,34.

1) Iontophoresis:

Iontophoresis is the use of harmless electric currents (0.1-1.0 mA/cm²) to drive charged medications into the skin by electrostatic attraction, allowing ionic pharmaceuticals to enter the body via their potential gradient^36,37,38. In contrast to other transdermal delivery systems, it also uses a second driving force: the electric potential gradient, which works in tandem with the concentration gradient across the skin^39,
40. This is important because uncharged substances can also be moved through electro osmosis (Fig. 3)

Figure 3: Iontophoresis patch with permission.

2) Ultrasound Devices:

Ultrasound is a type of sound wave that vibrates at various frequencies and has been used in numerous research fields, including physics, chemistry, biology, and engineering, for many years^41,42.

In ultrasound treatments, techniques like sonophoresis and phonophoresis are used to deliver medications through the skin. This is done by utilizing ultrasound waves that operate at frequencies between 20 kHz and 16 MHz. This technique employs intensity sufficient to lower the skin’s resistance^41,36. Using ultrasound to improve skin permeability can deliver a wide spectrum of medications, regardless of their electrical characteristics. This includes hydrophilic medicines and those with large molecular weights⁴³. However, the precise mechanism behind this effect remains unknown⁴². Ultrasound affects cells and tissues in two ways: thermally and through cavitation. These effects are caused by the collapse of cavitation bubbles and acoustic streaming, which can be defined as the vibration of these bubbles in an ultrasonic field³⁶. Ultrasound can heat the insonated medium, such as the skin, by converting sound waves with frequencies that are higher than the highest human hearing limit. Naturally, a higher absorption coefficient in the medium leads to a greater temperature rise and, consequently, a more significant thermal effect. Research indicates that cavitation is considered the primary mechanism that enhances transdermal drug delivery (TDD) through ultrasound treatment⁴².

3. SUSTAINED-RELEASE MECHANISM IN TRANSDERMAL DRUG DELIVERY SYSTEMS:

Transdermal drug delivery systems (TDDS) use sustained-release mechanisms to provide medications in a regulated and consistent manner over an extended period of time. The two main types of mechanisms employed are matrix systems and reservoir systems.

3.1 Reservoir system:

The medication reservoir in this transdermal system is positioned between a membrane that regulates the release rate and a water proof backing layer. This membrane can be either non-porous or microporous, depending on the design⁵. Only the rate-controlling membrane enables the medication to be released. It can be incorporated into a solid polymer matrix or present in the drug reservoir compartment as a solution, suspension, or gel. A hypoallergenic adhesive polymer can be applied as a smooth film between the release liner and the membrane, or in a concentric pattern on the membrane’s surface².

3.2 Matrix system:

3.2.1 Drug in adhesive system:

This procedure involves dissolving the medication in a polymer adhesive. To produce a drug reservoir. After that, the medicated adhesive polymer is applied onto a nonpermeable backing layer using methods like solvent casting or melting, especially for hot melt adhesives. To protect the reservoir, further layers of unmedicated sticky polymer are applied on top^2,45.

3.2.2 Matrix dispersion system:

The medication is equally distributed across a matrix of polymers that can repel or attract water. A disk carrying the medicine is then fastened to a base plate, keeping everything sealed off, using a backing material that prevents the drug from escaping. Rather than putting adhesive directly on the drug reservoir, it’s applied in a circular band around the edge, creating a sticky rim that holds everything in place^44,45.

3.3 Micro reservoir systems:

As a reservoir-matrix dispersion system, this TDDS performs the first step in creating the drug reservoir is to suspend the medication in a solution of water and a water soluble polymer. The mixture is then evenly placed into a lipophilic polymer. This method produces thousands of small, impermeable drug reservoir spheres. The dispersion, which is thermodynamically unstable, rapidly cross-links in situ^2,44,45.

Table 2: Comparison of Matrix and Reservoir Systems

Feature	Matrix Systems	Reservoir Systems
Drug Distribution	Uniformly distributed throughout the matrix	Stored in a reservoir
Release Mechanism	Diffusion through the matrix	Diffusion through a rate-controlling membrane
Release Profile	Can be less consistent over time	More consistent release rate
Manufacturing Complexity	Generally simpler	More complex due to the need for a membrane

4. PREPARATION METHOD FOR SYNTHESIS OF ZINC OXIDE

4.1 Structure:

Zinc and oxygen are from the periodic table’s second and sixth groups, respectively, making ZnO a renowned II-VI semiconductor material. ZnO semiconductor exhibits many desirable traits, such as high transparency, antimicrobial propertyand high mobility of electrons, large bandgap, high room temperature thermal and mechanical stability, and strong luminescence at room temperature. Its large bandgap of 3.37 eV places it between covalent and ionic semiconductors^46,47.

4.2 Preparation Technique:

Here, we present a concise overview of some of the most important methods for preparation and procurement of ZnO nanoparticles (ZnO-NPs). ZnO-NPs can be generated using various processes and circumstances. The selected method significantly influences the characteristics of the resulting zinc oxide particles, which can vary in morphology and size^48,49. Below, we outline the different methods available for preparing ZnO-NPs.

Table 3: ZnO nanoparticles synthesized using various techniques.

Techniques	Benefits	Drawbacks	References
Chemical synthesis	It is the most significant procedure and is performed with various precursors and under various settings. The size and shape of NPs fluctuate morphologically.	Compounds that may be hazardous are adsorbed on the surface.	50
Vapor transport synthesis	This approach is the most often used and has a comparatively mild growth temperature.	An imbalance in the ratio of vapor pressure may have an impact on the ZnO nanostructure.	51
Hydrothermal synthesis	The use of basic equipment, growth without catalysts, affordability, uniform production, environmental friendliness, and reduced toxicity.	A high temperature might be necessary to start.	52
Green synthesis	This is a low-cost, environmentally friendly method that eliminates the need for intermediate base groups.	Variable particle size and shape and potential for low yields and high costs.	53

4.3 Synthesis of Zinc Oxide Nanoparticles using Chemical Methods:

In Table 3, a description of some common method used for the synthesis of ZnO nanoparticles is provided.

4.3.1 Advantages of Chemical Methods:

This significant process can occur with a variety of precursors and is impacted by a number of variables, including temperature, time, and reactant concentration. Depending on the adjustment of these parameters, the shape and size of the resultant nanoparticles may change considerably. Below, let us discuss various chemical approaches to synthesizing ZnO nanoparticles.

4.3.2 Reaction of Zn and Alcohol:

Through a sequence of chemical processes, alcohol is essential to the creation of ZnO. Initially, ethanol is combined with a specific quantity of zinc powder. After a few minutes of high temperature heating, this mixture is allowed to cool at room temperature for two days. The finished product is then extracted by cleaning, centrifuging, and vacuum-drying the mixture. The formation of oxide particles happens gradually and is carefully managed in the alcoholic environment⁵⁴.

4.3.3 Vapor Transport Synthesis:

The simplest method employed is vapor transport. ZnO nanostructures form when zinc reacts with oxygen. There are infinite methods to produce ZnO vapor. Heating zinc powder with oxygen is a simple example, despite the comparatively low temperature needed for this procedure. For high-quality ZnO nanoparticles to form, the ratio of oxygen pressure to zinc vapor pressure

must be precisely maintained⁵⁵.

4.3.4 Hydrothermal synthesis:

This technique is excellent for efficiently adjusting particle size because it uses low temperatures. This process has some merits over the growth methods, including easy equipment, catalytic-free growth, less expensive, homogeneous fabrication, environment-friendly and less toxic, and is preferred by low reaction temperatures. This process is preferred by microelectronics because of low reaction temperatures. ZnO NPs and other fluorescent compounds have been successfully synthesized using this technique⁵⁶.

4.3.5 ZnO-NPs Green Synthesis:

As the demand for eco-friendly approaches continues to rise, various techniques have been explored to synthesize ZnO nanoparticles from a range of sources, including algae, bacteria, fungi, plants, and more. To show case the research done in this area, a series of tables has been compiled⁵⁷. Synthesis of biolistic nanoparticles is just one of the many ways to create particles using physical and chemical methods. Most researchers are now leaning towards green synthesis techniques for making metal and oxide nanoparticles. This plant-mediated approach to nanoparticle synthesis is not only quick and cost-effective but also environmentally friendly and safe for human consumption⁵⁸. We created zinc oxide nanoparticles (ZnO NPs) using the plant extract from Vitex negundo, commencing with zinc nitrate hexahydrate. Biosynthesized ZnO NPs shown antibacterial efficacy against Aureus bacteria and E. coli⁵⁹. Biogenic nanoparticles (NPs) can be safely synthesized using certain biological systems. However, using microorganisms for this process can be quite challenging because maintaining cell cultures, synthesizing them intracellularly, and going through multiple purification steps can be a real hassle. On the other hand, plant materials are a great choice for synthesizing zinc oxide (ZnO) NPs; thanks to the unique photochemical they produce. Extracting from plant parts is not only more affordable and eco-friendly, but it also doesn’t rely on middlemen⁶⁰.

4.3.6 Sol-Gel Technique:

Through a series of hydrolysis and polymerization procedures, a sol like solution of inorganic metallic salts is gradually transformed into a solid “gel” in the traditional approach for creating metal oxide nanoparticles. After that, the gel undergoes solvent evaporation and is heated to yield the final product^{61,62, 63}. The sol-gel process is visually represented in Fig 4. Using this method, we can create ZnO nanoparticles that resemble a fine powder, all while keeping a tight grip on their chemical composition^64,65. The process does come with some downsides, such as shrinkage, drying shrinkage cracks, and a lack of control over porosity⁶³. The protocol is straightforward to implement, and the materials can be prepared quickly, which is why it’s been well documented in the literature. Despite its drawbacks, this approach is widely used. We used ethanol and zinc acetate dehydrates (Zn (CH₃COO)₂. 2H₂O) as solvents to create rod-shaped ZnO nanoparticles, which had a size range of 81.28 to 84.98 nanometers⁶⁶. The progressive transformation of an aqueous solution of inorganic metallic salts into a solid “gel” phase is a common method for creating metal oxide nanoparticles.

A sequence of hydrolysis and polymerization events carry out this procedure. Once the gel is formed, it’s then subjected to solvent evaporation and heating to produce the final product^61,62,63. Fig 4. provides a clear schematic of the sol-gel process. Through this method, ZnO nanoparticles can be created in a fine powder form, allowing for precise control over their chemical composition^64,65. The process also has inherent limitations such as shrinkage, drying shrinkage cracking, and lack of control of porosity⁶³. As the protocol is simple to use and the significant material is developed in a rapid manner, the technique is heavily discussed in corresponding literature. It is one of the most popular techniques despite all its drawbacks. Zinc acetate dehydrates (Zn (CH₃COO)₂. 2H₂O) and ethanol were used as solvents to create rod-shaped ZnO-NPs with diameters ranging from 81.28 to 84.98 nanometers⁶⁶.

We created spherically shaped ZnO nanoparticles with an average diameter of 28 nm using the sol-gel process⁶⁷. Diethylene glycol (C₄H₁₀O₃) and zinc sulfate heptahydrate (ZnSO₄.7H₂O) were employed as surfactants during the production process. Additionally, we created ZnO nanoparticles (ZnO-NPs) with a particle size range of 12 to 30nm using a sol-gel technique with Zn (CH₃COO)₂.2H₂O as the precursor using a solution of ammonia and methanol. Consequently, 50–60nm diameter spherical ZnO-NPs were produced^65,68.

Figure 4: Diagrammatic representation of the procedures used in the sol-gel synthesis of ZnO-NPs

5. GREEN-SYNTHESIZED ZNO-NPS AND THEIR USE IN BIOMEDICINE:

In the last ten years, there’s been a noticeable in interest surrounding nanoparticle research, especially when it comes to their biological uses⁵⁹.

5.1 ZnO-NPs Anti-bacterial Activity:

The two most common categories of pharmacological medications are inorganic and organic. It has been demonstrated that organic medical medication molecules are less stable at high temperatures and pressures than inorganic ones⁷⁰. ZnO-NPs are superior pharmaceutical medications. Compared to micro particles, ZnO-NPs seem to have good pharmacological efficacy for therapy. Interestingly, it is impossible to fully explain the intricate mechanisms of pharmacological action⁷¹. ZnO-NPs exhibit therapeutic capabilities against spores that are resistant to heat and pressure, and they kill both gram-positive and gram-negative bacteria⁷². Experiments show that the range and concentration of ZnO-NPs affect their therapeutic effect, but not their crystalline structure or particle type. Thus, the more NPs there are, the better the medical care⁷³.

5.2 ZnO-NPs Anti-microbial Potential:

As a drug carrier, ZnO is being investigated at both the micro and nanoscales. Although drug-specific mechanisms are yet unknown, it has been proposed that zinc ion release, membrane rupture, ROS generated on the particle surface, and the surface area unit of the NPs are the common causes of cell swelling. ZnO-NPs’ therapeutic action is greatly impacted by high-temperature handling, while low-temperature handling decreases activity⁷⁴.

The MOA of ZnO-NPs medicament is unidentified. Although oxide formation has been postulated as a mechanism of action, particles-microorganism surface adhesion, through electrostatic attraction, has been proposed as a mechanism of ZnO-NPs medicament action. Chemiluminescence and oxygen electrode analysis can be used to do this. Extremely ionic, metal nanoparticles (NPs) can have a high surface and crystal content, as well as a variety of edge/corner and reactive surface site morphologies. One of the areas being studied in relation to treatment regimens with ablation regimens is the field of ZnO-NPs. By applying heat, NPs will create a medical specialty that is antineoplastic and has a synergistic anticancer impact, even if they have a stronger thermal effect on neoplasm ablation. They can even be demonstrated to provide suitable medical support. Several studies have demonstrated that the synthesis of NPs with the proper composition and properties to generate the ablation effect will be made possible by an understanding of the molecular process underpinning tumor-mediated NP ablation⁷⁵.

5.3 ZnO-NPs Anti-cancer Activity:

ZnO cancer nanotechnology possesses enormous promise for molecular recognition, molecular visualization, and individualized medical intervention based on nursing knowledge field subject matter area study in science, engineering, and medicines. In particular, semiconductor quantum dots and iron chemical complex nanocrystals are materials that possess optical, magnetic, or structural characteristics not present in molecules or bulk materials. When combined with antigen-targeting ligands like peptides or antibodies, these NPs can now be targeted against neoplasm antigens as biomarkers and neoplastic vasculature with high specificity and similarity. Because of their enormous surface areas and functional groups, NPs with diameters ranging from 5 to 100 nm can be conjugated to a wide variety of medicinal and diagnostic chemicals. With the aid of NP medications, a bioaffinity NPs to molecular and cellular imaging rectifier junction can offer customized medical therapy. Scientists have recently designed and suggested nano-devices in cancer screening and detection at early stages. Application of cancer biomarkers for cancer treatment and diagnosis through personalized molecular profile and genetically engineered and super-molecular biomarkers is enabled through developments in personalized medication⁷⁶.

6. CONCLUSION:

Utilizing zinc oxide nanoparticles (ZnO-NPs) in prolonged-release transdermal drug delivery systems (TDDS) offers an innovative approach to enhancing the stability, efficacy, and patient compliance of pharmaceuticals. ZnO-NPs offers various benefits, such as facilitated skin penetration, controlled release, and antimicrobial action. With the capacity for modifying drug diffusion through skin layers, they have prolonged therapeutic responses along with a reduction in systemic toxicity. Different synthesis routes, including green synthesis and sol-gel processes, have enabled custom ZnO-NPs with high biocompatibility and stability. Nonetheless, safety and regulatory compliance concerns regarding ZnO-NP-induced cytotoxicity and chronic exposure effects must be addressed to ensure safety. Despite these setbacks, ZnO-NPs remain potential effective carriers for TDDS and a possible alternative to traditional drug delivery systems.

Future studies need to aim at maximizing ZnO-NPs for enhanced biocompatibility and reducing possible toxicity. ZnO-NPs’ surface can be modified with biopolymers like polyethylene glycol (PEG) or chitosan to increase medication loading capacity and reduce skin hazard reactions. Additionally, the combination of ZnO-NPs with emerging technologies including microneedles, nanogels, and smart-responsive delivery carriers could transform TDDS into precision and tailored medicine strategies. Clinical trials for ZnO-NP-based TDDS in the field are necessary to secure regulatory approval and universal use. Further research into ZnO-NPs’ applicability for biologics’ transdermal delivery, such as peptides and vaccines, may also introduce new therapeutic options. With ongoing advancements, ZnO-NPs have the potential to revolutionize transdermal drug delivery and significantly improve patient outcomes.

7. REFERENCES:

1. Durga KN, Bhuvaneswari P, Hemalatha B, Padmalatha K. A review on transdermal drug delivery system. Asian Journal of Pharmacy and Technology. 2022; 12(2): 159-66. https://doi.org/10.52711/2231-5713.2022.00027

2. Rastogi V, Yadav P. Transdermal drug delivery system: An overview. Asian Journal of Pharmaceutics (AJP). 2012; 6(3). https://doi.org/10.22377/ajp.v6i3.51

3. Phaugat P, Dhall M, Nishal S. A Concise Outline on Innovative Permeation Enhancers in Transdermal Drug Delivery Approach. Indian Drugs. 2023 Aug 1; 60(8). https://doi.org/10.53879/id.60.08.12392

4. Das PS, Saha PU. Design and characterisation of transdermal patches of Phenformin hydrochloride. Int J Curr Pharm Res. 2017 Nov 14; 9(6): 90-3. http://dx.doi.org/10.22159/ijcpr.2017v9i6.23437

5. Naik A, Kalia YN, Guy RH. Transdermal drug delivery: overcoming the skin’s barrier function. Pharmaceutical science and technology today. 2000 Sep 1; 3(9): 318-26. https://doi.org/10.1016/S1461-5347(00)00295-9

6. Chandrashekar NS, Shobha Rani RH. Physicochemical and pharmacokinetic parameters in drug selection and loading for transdermal drug delivery. Indian J Pharm Sci. 2008 Jan; 70(1): 94-6. doi: 10.4103/0250-474X.40340. PMID: 20390089; PMCID: PMC2852070.

7. Merkle HP, Anders R, Wermerskirchen A. Mucoadhesive buccal patches for peptide delivery. In Bioadhesive Drug Delivery Systems 2024 Jan 1 (pp. 105-136). https://doi.org/10.1201/9781003574484-6

8. Brown L, Langer R. Transdermal delivery of drugs. Annual review of medicine. 1988; 39: 221-9. 10.1146/annurev.me.39.020188.001253

9. Benson HA. Transdermal drug delivery: penetration enhancement techniques. Current Drug Delivery. 2005 Jan 1; 2(1): 23-33. https://doi.org/10.2174/1567201052772915

10. Patil H, Patel N, Patil V, Rane B, Gujrathi N, Pawar S. A review on sustained release drug delivery system. International Journal Of Pharmaceutical, Chemical And Biological Sciences. 2014; 4(3): 470-8. 10.20959/wjpr20209-18370

11. Verma DK. Formulation and characterization of metformin hydrochloride sustained release matrix tablet containing Cassia tora mucilage. Journal of Drug Delivery and Therapeutics. 2017; 7(6): 66-75. http://dx.doi.org/10.22270/jddt.v7i6.1520

12. Singhal D, Curatolo W. Drug polymorphism and dosage form design: a practical perspective. Advanced drug delivery reviews. 2004 Feb 23; 56(3): 335-47. https://doi.org/10.1016/j.addr.2003.10.008

13. Brahmankar DM, Jaiswal SB. Biopharmaceutics and Pharmacokinetics: Pharmacokinetics, (2nd ed) Vallabh Prakashan, Delhi, 2009, 399-401.

14. E Leucuta S. Drug delivery systems with modified release for systemic and biophase bioavailability. Current Clinical Pharmacology. 2012 Nov 1; 7(4): 282-317. https://doi.org/10.2174/157488412803305786

15. Espitia PJ, Soares ND, Coimbra JS, de Andrade NJ, Cruz RS, Medeiros EA. Zinc oxide nanoparticles: synthesis, antimicrobial activity and food packaging applications. Food and Bioprocess Technology. 2012 Jul; 5: 1447-64. https://doi.org/10.1007/s11947-012-0797-6

16. Zhou X, Xu W, Liu G, Panda D, Chen P. Size-dependent catalytic activity and dynamics of gold nanoparticles at the single-molecule level. Journal of the American Chemical Society. 2010 Jan 1; 132(1): 138-46. https://doi.org/10.1021/ja904307n

17. Khan ZU, Sadiq HM, Shah NS, Khan AU, Muhammad N, Hassan SU, Tahir K, Khan FU, Imran M, Ahmad N, Ullah F. Greener synthesis of zinc oxide nanoparticles using Trianthema portulacastrum extract and evaluation of its photocatalytic and biological applications. Journal of Photochemistry and Photobiology B: Biology. 2019 Mar 1; 192: 147-57. https://doi.org/10.1016/j.jphotobiol.2019.01.013

18. Rasmussen JW, Martinez E, Louka P, Wingett DG. Zinc oxide nanoparticles for selective destruction of tumor cells and potential for drug delivery applications. Expert opinion on drug delivery. 2010 Sep 1; 7(9): 1063-77. https://doi.org/10.1517/17425247.2010.502560

19. Ryter SW, Kim HP, Hoetzel A, Park JW, Nakahira K, Wang X, Choi AM. Mechanisms of cell death in oxidative stress. Antioxidants and Redox Signaling. 2007 Jan 1; 9(1): 49-89. https://doi.org/10.1089/ars.2007.9.49

20. Montagna, W. The Structure and Function of Skin; Elsevier: Amsterdam, the Netherlands, 2012.

21. Brito S, Baek M, Bin BH. Skin structure, physiology, and pathology in topical and transdermal drug delivery. Pharmaceutics. 2024 Oct 31; 16(11): 1403. https://doi.org/10.3390/pharmaceutics16111403

22. Al-Khafaji Z, Brito S, Bin BH. Zinc and zinc transporters in dermatology. International Journal of Molecular Sciences. 2022 Dec 18; 23(24): 16165. https://doi.org/10.3390/ijms232416165

23. Verma DK. Formulation and characterization of metformin hydrochloride sustained release matrix tablet containing Cassia tora mucilage. Journal of Drug Delivery and Therapeutics. 2017; 7(6): 66-75. DOI: http://dx.doi.org/10.22270/jddt.v7i6.1520

24. Blanpain C, Fuchs E. Epidermal homeostasis: a balancing act of stem cells in the skin. Nature reviews Molecular Cell Biology. 2009 Mar; 10(3): 207-17. https://doi.org/10.1038/nrm2636

25. Bin BH, Joo YH, Lee AY, Shin SS, Cho EG, Lee TR. Novel inhibitory effect of N-(2-hydroxycyclohexyl) valiolamine on melanin production in a human skin model. International Journal of Molecular Sciences. 2014 Jul 9; 15(7): 12188-95. https://doi.org/10.3390/ijms150712188

26. Bin BH, Kim ST, Bhin J, Lee TR, Cho EG. The development of sugar-based anti-melanogenic agents. International Journal of Molecular Sciences. 2016 Apr 16; 17(4):583. https://doi.org/10.3390/ijms17040583

27. Souto EB, Fangueiro JF, Fernandes AR, Cano A, Sanchez-Lopez E, Garcia ML, Severino P, Paganelli MO, Chaud MV, Silva AM. Physicochemical and biopharmaceutical aspects influencing skin permeation and role of SLN and NLC for skin drug delivery. Heliyon. 2022 Feb 1; 8(2). https://doi.org/10.1016/j.heliyon.2022.e08938

28. Lai-Cheong JE, McGrath JA. Structure and function of skin, hair and nails. Medicine. 2013 Jun 1; 41(6): 317-20. https://doi.org/10.1016/j.mpmed.2013.04.017

29. Jabłonska S, Majewski S, Obalek S, Orth G. Cutaneous warts. Clinics in Dermatology. 1997 May 1; 15(3): 309-19. https://doi.org/10.1016/S0738-081X(96)00170-8

30. Schuetz YB, Naik A, Guy RH, Kalia YN. Emerging strategies for the transdermal delivery of peptide and protein drugs. Expert Opinion on Drug Delivery. 2005 May 1; 2(3):533-48. https://doi.org/10.1517/17425247.2.3.533

31. Schoellhammer CM, Blankschtein D, Langer R. Skin permeabilization for transdermal drug delivery: recent advances and future prospects. Expert Opinion on Drug Delivery. 2014 Mar 1; 11(3):393-407. https://doi.org/10.1517/17425247.2014.875528

32. Shahzad Y, Louw R, Gerber M, Du Plessis J. Breaching the skin barrier through temperature modulations. Journal of Controlled Release. 2015 Mar 28; 202: 1-3. https://doi.org/10.1016/j.jconrel.2015.01.019

33. Zaid Alkilani A, McCrudden MT, Donnelly RF. Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics. 2015 Oct 22; 7(4): 438-70. https://doi.org/10.3390/pharmaceutics7040438

34. HS V, Krishna KR, Parthiban S, Anupama HB. Microsponge gel in transdermal delivery: a comprehensive review of its role, benefits, enhanced skin penetration and efficacy. World Journal of Pharmaceutical Research. 202; 14(7): 599-613. 10.20959/wjpr20257-36093

35. Sugibayashi K, Morimoto Y. Polymers for transdermal drug delivery systems. Journal of Controlled Release. 1994 Feb 1; 29(1-2):177-85. https://doi.org/10.1016/0168-3659(94)90134-1

36. Schoellhammer CM, Blankschtein D, Langer R. Skin permeabilization for transdermal drug delivery: recent advances and future prospects. Expert opinion on drug delivery. 2014 Mar 1; 11(3): 393-407. https://doi.org/10.1517/17425247.2014.875528

37. Gratieri T, Alberti I, Lapteva M, Kalia YN. Next generation intra-and transdermal therapeutic systems: using non-and minimally-invasive technologies to increase drug delivery into and across the skin. European Journal of Pharmaceutical Sciences. 2013 Dec 18; 50(5): 609-22. https://doi.org/10.1016/j.ejps.2013.03.019

38. Lakshmanan S, Gupta GK, Avci P, Chandran R, Sadasivam M, Jorge AE, Hamblin MR. Physical energy for drug delivery; poration, concentration and activation. Advanced drug delivery reviews. 2014 May 1; 71: 98-114. https://doi.org/10.1016/j.addr.2013.05.010

39. Schoellhammer CM, Blankschtein D, Langer R. Skin permeabilization for transdermal drug delivery: recent advances and future prospects. Expert Opinion on Drug Delivery. 2014 Mar 1; 11(3): 393-407. https://doi.org/10.1517/17425247.2014.875528

40. Gratieri T, Kalia YN. Mathematical models to describe iontophoretic transport in vitro and in vivo and the effect of current application on the skin barrier. Advanced Drug Delivery Reviews. 2013 Feb 1; 65(2): 315-29. https://doi.org/10.1016/j.addr.2012.04.012

41. Han T, Das DB. Potential of combined ultrasound and microneedles for enhanced transdermal drug permeation: a review. European Journal of Pharmaceutics and Biopharmaceutics. 2015 Jan 1; 89: 312-28. https://doi.org/10.1016/j.ejpb.2014.12.020

42. Azagury A, Khoury L, Enden G, Kost J. Ultrasound mediated transdermal drug delivery. Advanced Drug Delivery Reviews. 2014 Jun 15; 72: 127-43. https://doi.org/10.1016/j.addr.2014.01.007

43. Park D, Park H, Seo J, Lee S. Sonophoresis in transdermal drug deliverys. Ultrasonics. 2014 Jan 1; 54(1):56-65. https://doi.org/10.1016/j.ultras.2013.07.007

44. Choudhary N, Singh AP, Singh AP. Transdermal drug delivery system: A review. Indian J. Pharm. Pharmacol. 2021; 8(1): 5-9. https://doi.org/10.18231/j.ijpp.2021.002

45. Brahmankar DM, Jaiswal SB. Biopharmaceutics and pharmacokinetics A Treatise. Delhi: Vallabh Prakashan; 1995; 335-71.

46. Rai-Kalal P, Jajoo A. Priming with zinc oxide nanoparticles improve germination and photosynthetic performance in wheat. Plant Physiology and Biochemistry. 2021 Mar 1; 160: 341-51. https://doi.org/10.1016/j.plaphy.2021.01.032

47. Brayner R, Ferrari-Iliou R, Brivois N, Djediat S, Benedetti MF, Fiévet F. Toxicological impact studies based on Escherichia coli bacteria in ultrafine ZnO nanoparticles colloidal medium. Nano letters. 2006 Apr 12; 6(4): 866-70. https://doi.org/10.1021/nl052326h

48. Wojnarowicz J, Chudoba T, Lojkowski W. A review of microwave synthesis of zinc oxide nanomaterials: Reactants, process parameters and morphologies. Nanomaterials. 2020 May 31; 10(6): 1086. https://doi.org/10.3390/nano10061086

49. Noman MT, Amor N, Petru M. Synthesis and applications of ZnO nanostructures (ZONSs): A review. Critical Reviews in Solid State and Materials Sciences. 2022 Mar 4; 47(2): 99-141. https://doi.org/10.1080/10408436.2021.1886041

50. Hudlikar M, Joglekar S, Dhaygude M, Kodam K. Latex-mediated synthesis of ZnS nanoparticles: green synthesis approach. Journal of Nanoparticle Research. 2012 May; 14: 1-6. https://doi.org/10.1007/s11051-012-0865-x

51. Kong XY, Wang ZL. Spontaneous polarization-induced nanohelixes, nanosprings, and nanorings of piezoelectric nanobelts. Nano letters. 2003 Dec 10; 3(12): 1625-31. https://doi.org/10.1021/nl034463p

52. Lee CY, Tseng TY, Li SY, Lin P. Effect of phosphorus dopant on photoluminescence and field-emission characteristics of Mg0. 1Zn0. 9O nanowires. Journal of Applied Physics. 2006 Jan 15; 99(2). https://doi.org/10.1063/1.2161420

53. Heinlaan M, Ivask A, Blinova I, Dubourguier HC, Kahru A. Toxicity of nanosized and bulk ZnO, CuO and TiO2 to bacteria Vibrio fischeri and crustaceans Daphnia magna and Thamnocephalus platyurus. Chemosphere. 2008 Apr 1; 71(7):1308-16. https://doi.org/10.1016/j.chemosphere.2007.11.047

54. Ruchika AK. Performance analysis of Zinc oxide based alcohol sensors. Int. J. Appl. Sci. Eng. Res. 2015; 4(4):428-36. 10.6088.ijaser.04042

55. Kong XY, Wang ZL. Spontaneous polarization-induced nanohelixes, nanosprings, and nanorings of piezoelectric nanobelts. Nano letters. 2003 Dec 10; 3(12):1625-31. https://doi.org/10.1021/nl034463p

56. Lee CY, Tseng TY, Li SY, Lin P. Effect of phosphorus dopant on photoluminescence and field-emission characteristics of Mg0. 1Zn0. 9O nanowires. Journal of Applied Physics. 2006 Jan 15; 99(2). https://doi.org/10.1063/1.2161420

57. Bhat JA, Faizan M, Bhat MA, Huang F, Yu D, Ahmad A, Bajguz A, Ahmad P. Defense interplay of the zinc-oxide nanoparticles and melatonin in alleviating the arsenic stress in soybean (Glycine max L.). Chemosphere. 2022 Feb 1; 288:132471. https://doi.org/10.1016/j.chemosphere.2021.132471

58. Mahmoud AW, Abdeldaym EA, Abdelaziz SM, El-Sawy MB, Mottaleb SA. Synergetic effects of zinc, boron, silicon, and zeolite nanoparticles on confer tolerance in potato plants subjected to salinity. Agronomy. 2019 Dec 21; 10(1):19.https://doi.org/10.3390/agronomy10010019

59. Ambika S, Sundrarajan M. Antibacterial behaviour of Vitex negundo extract assisted ZnO nanoparticles against pathogenic bacteria. Journal of Photochemistry and Photobiology B: Biology. 2015 May 1; 146:52-7. https://doi.org/10.1016/j.jphotobiol.2015.02.020

60. Semida WM, Abdelkhalik A, Mohamed GF, Abd El-Mageed TA, Abd El-Mageed SA, Rady MM, Ali EF. Foliar application of zinc oxide nanoparticles promotes drought stress tolerance in eggplant (Solanum melongena L.). Plants. 2021 Feb 23; 10(2):421. https://doi.org/10.3390/plants10020421

61. Somiya, S. Handbook of Advanced Ceramics: Materials, Applications, Processing, and Properties, 2^nded.; Academic Press: Cambridge, MA, USA; Elsevier: Amsterdam, The Netherlands, 2013; 1–1229.

62. Bokov D, Turki Jalil A, Chupradit S, Suksatan W, Javed Ansari M, Shewael IH, Valiev GH, Kianfar E. Nanomaterial by sol‐gel method: synthesis and application. Advances in Materials Science and Engineering. 2021; 2021(1):5102014. https://doi.org/10.1155/2021/5102014

63. Simon V, Cavalu S, Simon S, Mocuta H, Vanea E, Prinz M, Neumann M. Surface functionalisation of sol–gel derived aluminosilicates in simulated body fluids. Solid State Ionics. 2009 May 29; 180(9-10):764-9. https://doi.org/10.1016/j.ssi.2009.02.011

64. Carter, B.C.; Norton, M.G. Ceramic Materials: Science and Engineering; 2013. http://ir.mksu.ac.ke/handle/123456780/6227

65. Al Abdullah K, Awad S, Zaraket J, Salame C. Synthesis of ZnO nanopowders by using sol-gel and studying their structural and electrical properties at different temperature. Energy Procedia. 2017 Jul 1; 119:565-70. https://doi.org/10.1016/j.egypro.2017.07.080

66. Hasnidawani JN, Azlina HN, Norita H, Bonnia NN, Ratim S, Ali ES. Synthesis of ZnO nanostructures using sol-gel method. Procedia Chemistry. 2016 Jan 1; 19:211-6. https://doi.org/10.1016/j.proche.2016.03.095

67. Alwan RM, Kadhim QA, Sahan KM, Ali RA, Mahdi RJ, Kassim NA, Jassim AN. Synthesis of zinc oxide nanoparticles via sol–gel route and their characterization. Nanosci. Nanotechnol. 2015; 5(1):1-6. DOI: 10.5923/j.nn.20150501.01

68. Hasnidawani JN, Azlina HN, Norita H, Bonnia NN, Ratim S, Ali ES. Synthesis of ZnO nanostructures using sol-gel method. Procedia Chemistry. 2016 Jan 1; 19:211-6. https://doi.org/10.1016/j.proche.2016.03.095

69. Burgess R. Medical applications of nanoparticles and nanomaterials. InStrategy for the Future of Health 2009 (pp. 257-283). IOS Press. 10.3233/978-1-60750-050-6-257

70. Zhang L, Jiang Y, Ding Y, Daskalakis N, Jeuken L, Povey M, O’neill AJ, York DW. Mechanistic investigation into antibacterial behaviour of suspensions of ZnO nanoparticles against E. coli. Journal of Nanoparticle Research. 2010 Jun; 12:1625-36. https://doi.org/10.1007/s11051-009-9711-1

71. Huang Z, Zheng X, Yan D, Yin G, Liao X, Kang Y, Yao Y, Huang D, Hao B. Toxicological effect of ZnO nanoparticles based on bacteria. Langmuir. 2008 Apr 15; 24(8):4140-4. https://doi.org/10.1021/la7035949

72. Limbach LK, Wick P, Manser P, Grass RN, Bruinink A, Stark WJ. Exposure of engineered nanoparticles to human lung epithelial cells: influence of chemical composition and catalytic activity on oxidative stress. Environmental Science and Technology. 2007 Jun 1; 41(11):4158-63. https://doi.org/10.1021/es062629t

73. Husseiny MI, Abd El-Aziz M, Badr Y, Mahmoud MA. Biosynthesis of gold nanoparticles using Pseudomonas aeruginosa. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2007 Jul 1; 67(3-4):1003-6. https://doi.org/10.1016/j.saa.2006.09.028

74. Wang X, Chen H, Zheng Y, Ma M, Chen Y, Zhang K, Zeng D, Shi J. Au-nanoparticle coated mesoporous silica nanocapsule-based multifunctional platform for ultrasound mediated imaging, cytoclasis and tumor ablation. Biomaterials. 2013 Mar 1; 34(8):2057-68. https://doi.org/10.1016/j.biomaterials.2012.11.044

75. Ramamurthy CH, Sampath KS, Arunkumar P, Kumar MS, Sujatha V, Premkumar K, Thirunavukkarasu C. Green synthesis and characterization of selenium nanoparticles and its augmented cytotoxicity with doxorubicin on cancer cells. Bioprocess and Biosystems Engineering. 2013 Aug; 36:1131-9. https://doi.org/10.1007/s00449-012-0867-1

76. Nie S, Xing Y, Kim GJ, Simons JW. Nanotechnology applications in cancer. Annu. Rev. Biomed. Eng. 2007 Aug 15; 9(1):257-88. https://doi.org/10.1146/annurev.bioeng.9.060906.152025

Received on 24.05.2025 Revised on 09.09.2025

Accepted on 15.11.2025 Published on 22.01.2026

Available online from January 29, 2026

Asian J. Pharm. Res. 2026; 16(1):51-60.

DOI: 10.52711/2231-5691.2026.00007

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.