Microneedle: An Emerging Technique of Drug Delivery System

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Technical Review Article | Open Access | Published 16th December 2025

Microneedle: An Emerging Technique of Drug Delivery System

Abstract

Microneedles (MNs), a transdermal drug delivery system that combines the technology of transdermal patches and hypodermic needles, have been the subject of research and development in recent years. Getting medicine or other helpful substances through the skin is not easy because the outermost layer, called the stratum corneum, blocks most things from getting through. Because of this, scientists have been working on better ways to deliver treatments deep into the skin.

Microneedles offer several benefits over traditional methods like creams or injections. They’re easy to use, don’t usually cause pain, and people can apply them by themselves at home. Plus, they can be designed to release medicine quickly or slowly over time.

There are different types of microneedles which can be fabricated such as: solid, dissolving, hydrogel, coated and hollow etc. Selection of method of fabrication usually depends on the type and material of the microneedle. There is broader scope and significance of this system extending to many fields such as cancer, vaccine delivery, insulin delivery and cosmetics. From last few years, many microneedle products are available in the market. A lot of work and research needs to be done to overcome the challenges and this may also improve the performance of microneedles.

These tiny tools are being used in many areas, including drug delivery, vaccines, beauty treatments, medical testing, cancer research, healing wounds, and more.

Keywords: Microneedle, Fabrication, bioactive molecules Coated and dissolved microneedle.

1. INTRODUCTION

In the last ten years, there has been a lot of progress in understanding and treating pain, thanks to ongoing research into how pain works and how medicines can help. However, the common ways to deliver pain relief – such as taking pills, getting injections, or applying creams - often come with side effects, especially when used for a long time. Many patients also find these methods uncomfortable or inconvenient, leading to poor follow-through with treatment. Injections are especially disliked because they can cause pain and irritation. On the other hand, delivering medicine through the skin (topically) seems easier, but the skin itself is a tough barrier. It has three main layers: The stratum corneum (outermost layer), the epidermis (middle layer), and the dermis (deepest and thickest layer).

Among these, the stratum corneum is the main obstacle - it only lets very small, fat-loving (lipophilic) molecules pass through. Because of this, developing effective skin-based (topical) treatments can be difficult due to limited absorption through the skin¹,². To improve how well medicines pass through the skin, researchers have explored several topical and transdermal drug delivery methods, such as creams with nanoparticles, transdermal patches, microneedles, and microneedle patches. These systems are being studied to overcome the problems seen with traditional ways of giving medicine, such as pills or injections³.

Among these, transdermal drug delivery is becoming a popular and effective approach, especially for pain relief. It’s a non-invasive method, meaning it doesn’t require needles or surgery, and patients generally prefer it. In particular, microneedles (MNs) are attracting a lot of interest because they are cost-effective and can deliver medicine deep into the skin's dermal layer, making them especially useful for managing pain⁴. Microneedles are made up of many tiny needles. Their size can vary - usually 150 to 1500 micrometers (µm) long, 50 to 250 µm wide at the base, and 1 to 25 µm at the tip. These small dimensions make them ideal for delivering larger drug molecules effectively to the target area, offering excellent drug absorption through the skin⁵.

2. TRADITIONAL DRUG DELIVERY SYSTEMS

Most traditional treatments used for managing pain have some serious drawbacks. These include the need to increase doses over time and the risk of harmful effects throughout the body. Taking painkillers or anti-inflammatory drugs by mouth is simple and convenient, but it also has some limitations such as needing to take them often, delayed pain relief, short-lasting effects, high doses, irritation in the stomach and intestines, and low absorption into the body⁶.

NSAIDs (non-steroidal anti-inflammatory drugs) are commonly used to treat pain and inflammation. But studies show that people who regularly take NSAIDs have a 14–25% chance of developing stomach or intestinal ulcers, which is 2 to 6 times higher than those who don’t use them⁷.

Injections (parenteral administration) are not ideal for daily pain management because they can cause harmful effects in the body and may lead to infections at the injection site. Also, people often experience needle-related anxiety, pain, or even fainting, making this method uncomfortable and poorly accepted⁸.

Topical treatments (such as creams or gels applied to the skin) are receiving more attention because they are easy to use, generally safe, and cause fewer side effects throughout the body. But these also have limits- they don’t pass through the skin very well, often need to be used frequently, and can cause skin irritation when used for a long time⁹,¹⁰.

This method also allows controlled release of the drug, which is helpful for chronic pain. It can reduce the risk of drug abuse and improve long-term pain relief¹¹. However, traditional transdermal patches often don’t release enough drug to reach the required levels in the blood, which can make them less effective. Their performance depends on factors such as the drug’s chemical properties, how much drug is loaded, how well it diffuses, and the materials used in the patch. Because of these limitations, better drug delivery systems are needed to improve pain and inflammation treatment¹².

3. MICRONEEDLES AS A REVOLUTIONARY APPROACH

Traditional pain treatments often cause side effects and are not suitable for long-term use because patients tend to stop using them due to discomfort or inconvenience. However, recent advances in drug delivery technologies have significantly improved how diseases are detected, treated, and prevented¹².

To address the drawbacks of conventional treatments and improve patient comfort and compliance, microneedles (MNs) have emerged as a promising new option for managing pain and inflammation. MNs combine the benefits of hypodermic injections (which are effective but painful) and transdermal patches (which are painless but sometimes ineffective). This hybrid system offers a simple, safe, and painless method of delivering medicine¹³,¹⁴. MNs provide several key benefits: Fast action (quick onset of relief), Precise dosing, Avoidance of first-pass metabolism (which occurs in the liver and reduces drug effectiveness), High drug bioavailability (more of the drug reaches the bloodstream)¹⁵,¹⁶. Because of these advantages, microneedles are becoming a fast-growing and widely accepted technology in drug delivery¹⁷.

One of the standout features of MNs is their ability to deliver pain relief quickly and effectively, making them ideal for conditions that require long-term treatment. They are also easy to use at home, reducing the need for frequent doctor visits and lowering the risk of side effects or drug overdose.

For example, traditional lidocaine creams, used for pain relief, need to be applied for 60 to 120 minutes to work, and they only provide pain relief for 30 to 60 minutes. In contrast, lidocaine-coated microneedles can provide the same effect with just a 1 to 5-minute application- a major improvement in both speed and convenience¹⁸,¹⁹.

4. MICRONEEDLE FABRICATION MATERIALS:

4.1 Silicon: The first microneedles were developed in the 1990s and were made from silicon. Silicon is a crystalline material with isotropic properties, meaning its behavior depends on how its crystal structure is aligned. This gives it a wide range of flexibility in terms of strength, with elastic moduli ranging from 50 to 180 GPa. Because of this, silicon can be used to create microneedles in different shapes and sizes, making it a very versatile material.

Silicon can also be precisely manufactured and is suitable for mass production, and its low cost is another benefit. However, there are some drawbacks. Making silicon microneedles takes a lot of time, and more importantly, there are biocompatibility concerns. Since silicon is brittle, small fragments could break off and stay in the skin, potentially causing serious health problems²⁰,²¹.

4.2 Metal: The most commonly used metals for microneedle fabrication are stainless steel and titanium, while palladium, nickel, and palladium-cobalt alloys are also used. Metals are favoured due to their high strength and good biocompatibility, making them more durable and reliable than brittle materials such as silicon. Stainless steel was the first metal used to make microneedles, and titanium has since emerged as a strong and effective alternative²².

4.3 Ceramic: Ceramics, especially alumina (Al₂O₃), are valued for their chemical resistance. Alumina forms a stable oxide structure due to strong ionic and covalent bonds between aluminum and oxygen atoms. Other ceramics such as gypsum (CaSO₄·2H₂O) and brushite (CaHPO₄·2H₂O) are also used. More recently, a special type of ceramic called Ormocer® (organically modified ceramic) has been introduced. This is a three-dimensionally cross-linked copolymer, meaning different properties can be achieved by altering the organic building blocks during synthesis. Ceramics are typically shaped using micro-moulding, where ceramic slurry is poured into molds. This method is efficient and suitable for scale-up production²³,²⁴.

4.4 Silica Glass: Silica glass is biocompatible and inert, but it is also brittle, making it prone to breaking. A more flexible version, Type I borosilicate glass (made from silica and boron trioxide), offers better elasticity. However, glass microneedles are not used commercially anymore and are mainly used for experimental purposes²⁰,²¹.

4.5 Carbohydrates: Carbohydrates, such as maltose, mannitol, trehalose, sucrose, xylitol, and galactose, can be used to make microneedles. These are often moulded using silicon or metal templates. A drug-loaded carbohydrate slurry is poured into the moulds, and the controlled dissolution of the sugar in the skin allows for regulated drug release. Carbohydrates are inexpensive and safe, but they degrade at high temperatures, making the fabrication process challenging²⁵.

4.6 Polymers: Various biodegradable and biocompatible polymers are widely used in microneedle production, including PMMA (poly methyl methacrylate), PLA (polylactic acid), PLGA (poly lactic-co-glycolic acid), PGA (poly glycolic acid), Polycarbonate, Cyclic olefin copolymer, PVP (polyvinyl pyrrolidone), PVA (polyvinyl alcohol), PS (polystyrene). These polymers are used for both solid microneedles and hydrogel-forming microneedle arrays. While not as mechanically strong as metal or silicon microneedles, they are more flexible and less brittle than glass or ceramic, making them suitable for safe and comfortable use²⁴,²⁶,²⁷.

5. TYPES OF MICRONEEDLES:

Microneedles (MNs) come in various forms, each designed to improve how drugs are delivered through the skin. The main types are:

5.1 Solid Microneedles (SMNs)

Solid microneedles are the earliest and simplest type, often used to pre-treat the skin. When inserted, they create tiny channels or pores in the skin’s outer layers. After removal, drugs can be applied over the treated area through a patch – a method known as “poke and patch. These

pores allow improved absorption of medications into the skin. The design of SMNs (shape, depth, and diameter) is critical to ensuring effective and safe penetration. While they help in drug delivery, the limited absorption through the small pores sometimes makes the method less efficient²⁰,²⁹.

5.2 Hollow Microneedles (HMNs)

Hollow microneedles resemble miniature hypodermic needles. They have a central hollow channel through which drugs are delivered directly into the skin. A pressure-based device controls the flow of the medication.

These microneedles are especially useful for large molecules like proteins, vaccines, and nucleotides, which are otherwise difficult to deliver through the skin. The ability to control flow allows for precise and targeted drug delivery³⁰.

5.3 Coated Microneedles (CMNs) and Dissolving Microneedles (DMNs)

Coated Microneedles (CMNs) have a drug-coated outer layer. When inserted into the skin, the coating dissolves in contact with body fluids, releasing the drug quickly.

For example, bleomycin-coated MNs are used for wart treatment, offering a painless and efficient alternative. CMNs are also being tested for peanut allergy therapy and eye diseases, showing promising results in modulating immune responses.

Dissolving Microneedles (DMNs) are made from biodegradable polymers that contain the drug within the microneedle. After insertion, the needles dissolve in the skin, releasing the drug in a controlled manner.

The choice of polymer is essential to ensure mechanical strength, biocompatibility, and controlled release. Since the needle dissolves entirely, there is no residue or waste left behind³¹,³².

5.4 Hydrogel-Forming Microneedles

These microneedles are made from swelling polymers (hydrogels) and are paired with a drug reservoir (such as a patch or tablet). When inserted into the skin, the microneedles absorb interstitial fluid and swell, creating microchannels that connect the drug reservoir to the skin tissue. This setup allows for continuous and sustained drug delivery over time. The hydrogel's structure allows it to hold and transport large quantities of drug efficiently, making it ideal for long acting and localized treatments¹⁸,³¹,³².

6. APPLICATION OF MICRONEEDLE DRUG DELIVERY SYSTEM

Microneedle (MN) technology has opened new possibilities in transdermal drug delivery. It is increasingly used in treating genetic disorders, various cancers, infectious diseases, and for vaccination. Compared to traditional microinjection, microneedles can treat multiple cells simultaneously, enabling both local and systemic delivery of bioactive agents. Future research should focus on using MNs in therapies for viral infections, diabetes, genetic disorders, oncological treatments, osteoporosis, and dermatological conditions³³.

6.1 Microneedles in Cosmetics

The skin’s main protective layer, the stratum corneum (10–20 µm thick), blocks the penetration of most substances. Microneedle patches (MNPs) are designed to create micro-scale pores that allow painless and effective drug or cosmetic agent delivery.

MNPs typically consist of arrays of 100 to 10,000 microneedles per cm², each 100–1,000 µm in length. These are either solid and coated with active ingredients or made from dissolvable polymers that encapsulate the drug³⁴,³⁵.

Microneedles are used for non-surgical cosmetic treatments, such as Anti-aging (wrinkles, sagging skin), Scar reduction (acne, surgical scars), Hyperpigmentation (age spots), and Hair loss (alopecia). They promote skin healing and rejuvenation without damaging the epidermis³⁴.

6.2 Microneedles in Cancer Therapy

Recent innovations have shown that MNs can enhance immunotherapy delivery for cancer by targeting the immune system instead of directly attacking tumors. For example, microneedle patches have been explored to deliver immunotherapeutic agents with improved accuracy and reduced side effects.

The Centers for Disease Control (CDC) is also evaluating MNs as a potential breakthrough for diseases such as measles through easy-to-use patches³⁶.

6.3 Microneedles in Myocardial Infarction (Heart Attack)

Microneedle patches embedded with cardiac stromal cells (MN-CSCs) have shown promise in heart regeneration after a myocardial infarction (MI). In rat models, these patches significantly improved cardiac function and angiogenesis (formation of new blood vessels). In porcine models, MN-CSC patches were safe and helped preserve heart function post-MI. This represents a novel, minimally invasive technique for cell-based heart repair³⁷,³⁸.

6.4 Microneedles in Pain Management

A new class of analgesic microneedle (AMN) patches has been developed for targeted, painless pain relief, especially for neuropathic pain. These dissolving microneedles deliver CGRP antagonist peptides directly into the skin. Animal studies (rats) show significant pain reduction without affecting normal motor function or causing side effects like skin irritation. AMN patches may offer a safer, more effective alternative to conventional pain medications³⁸,³⁹.

6.5 Microneedles in Rheumatoid Arthritis (RA)

RA is a chronic autoimmune disease involving joint inflammation, pain, and eventual joint damage. It is linked with pro-inflammatory cytokines (TNF-α, IL-1, IL-6), anti-citrullinated protein antibodies and epigenetic factors. Due to the strong skin barrier, delivering biological drugs through traditional transdermal methods is challenging.

Microneedles allow targeted delivery of anti-inflammatory agents to inflamed joints, helping to reduce joint inflammation, minimize synovial membrane thickening and improve treatment effectiveness³⁸,⁴⁰.

6.6 Microneedles in Atopic Dermatitis (AD)

Atopic dermatitis is primarily driven by genetic factors and involves epidermal barrier dysfunction, immune dysregulation, and altered skin microbiome. Microneedles offer a minimally invasive solution to deliver therapeutic agents directly into affected skin layers. This helps to manage inflammation, itching and skin barrier repair. Studies have demonstrated MNs' utility in a wide range of applications including drug delivery, vaccine administration, tissue regeneration, cancer diagnosis, and wound healing⁴¹,⁴².

Table 1. Approved Microneedle Products⁴³,⁴⁴,⁴⁵

Product name	Company name	Description of the product	Uses
Dermaroller®	Dermaroller® Germany, White Lotus.	A cylindrical roller with solid or metal microneedles, 0.2–2.5 mm in length.	Improve skin texture, treat scars and hyper pigmentation.
C-8 (Cosmetic type)	The Dermaroller Series by Anastassakis K.	A needle length of only 0.13 mm (130 μm).	Used to enhance penetration of topical agents.
CIT-8 (Collagen Induction Therapy	The Dermaroller Series by Anastassakis K.	A needle length of 0.5 mm (500 μm)	Used in collagen induction and skin remodeling.
MF-8 type	The Dermaroller Series by Anastassakis K.	A needle length of 1.5 mm (1500 μm)	Treat scars.
MS-4	The Dermaroller Series by Anastassakis K.	A Small cylinder, 1 cm length, 2 cm diameter, and 4 circular arrays of needles which are 1.5 mm in length	Used on facial acne scars.
MicroHyala®	CosMed transdermal drug deliver	Dissolving microneedle patch with hyaluronic acid	Wrinkle treatment
LiteClear®	Nanomed skincare	Solid silicon microneedles are used as pre-treatment and then drug applied topically.	Treats acne and skin blemishes

7. CHALLENGES AND LIMITATIONS

While microneedle (MN) technology shows great promise for transdermal pain management, most MN systems are still in early developmental stages and require extensive research, optimization, and clinical validation before widespread clinical application. Although the potential for MNs in controlled drug delivery has been established, several critical barriers must be addressed for successful translation from bench to bedside.

7.1 Technical and Mechanical Challenges

Mechanical Strength: Dissolvable polymeric MNs offer biocompatibility and safety but often lack the mechanical robustness of solid metal microneedles, making them prone to breakage or inadequate skin penetration.

Durability and Corrosion: Hollow stainless steel microneedles, though stronger, may be susceptible to corrosion over time, potentially leading to safety concerns.

Material Selection: Solid metal microneedles (e.g., stainless steel) can cause skin irritation or entrap metallic fragments. Metals and silicon, though generally inert and minimally immunogenic, are non-biodegradable, and may leave sharp remnants in tissue. Carbohydrate-based microneedles, often used for delivering delicate biologics, are highly sensitive to sterilization methods, which can alter their morphology, mechanical integrity, and physicochemical stability.

7.2 Biological and Application-Related Issues

Skin Reactions: The repetitive application of MNs can cause microbiological contamination, leading to skin allergies, redness, or irritation.

Dose Limitation: MNs typically carry a small quantity of drug, which may not suffice for conditions requiring higher systemic concentrations.

Uncontrolled Delivery: Achieving precise and consistent drug release remains a challenge, especially in hollow and coated microneedles, where flow and diffusion may vary.

Site-Specific Application: MN performance can vary depending on skin thickness and anatomical location, necessitating careful consideration during application.

Repeated Use Concerns: Frequent or prolonged use of MNs at the same site may lead to localized tissue stress or reduced effectiveness. Despite these limitations, the continued advancement of materials science, fabrication techniques, and biocompatibility assessments may soon overcome these barriers. Once optimized for mechanical strength, biocompatibility, sterilization tolerance, and dose efficiency, microneedle technology could become a superior, non-invasive alternative for managing chronic pain conditions such as neuropathic pain, rheumatoid arthritis, osteoarthritis, psoriatic arthritis, and atopic dermatitis. These conditions impact millions globally, making it crucial to develop effective, targeted, and user-friendly therapeutic options⁴⁴,⁴⁶,⁴⁷.

8. EMERGING INNOVATIONS AND FUTURE PROSPECTS

The field of microneedle (MN) technology is rapidly advancing, with novel and innovative concepts being introduced to overcome current limitations and enhance therapeutic outcomes. One of the primary challenges in transdermal delivery is the inefficient transport of hydrophilic and high-molecular-weight drugs across the skin barrier. Effective delivery of such agents requires MNs with optimized mechanical strength and insertion force, making material selection a critical factor in MN design and fabrication¹². A key consideration in MN development is the balance between drug permeability and patient comfort. Since insertion depth is directly correlated with pain, achieving optimal skin penetration with minimal discomfort is a central objective in MN research. To further enhance drug permeation, combinatorial approaches such as ultrasound-assisted transdermal delivery are being explored, offering promising synergy with MN systems⁵.

Role of 3D Printing in MN Fabrication: Recent progress in 3D printing technologies, particularly in techniques such as Fused Deposition Modeling (FDM) and Stereolithography (SLA), has revolutionized the fabrication of microneedles⁴⁸. These technologies allow for the creation of high-precision, customizable MN designs, enabling personalized treatment strategies tailored to specific pathological tissues. This customization paves the way for personalized medicine, potentially improving patient outcomes and reducing systemic side effects⁴⁹.

Conclusion

In recent years, there has been remarkable progress in the development and application of microneedle (MN) technologies, not only in terms of material compositions and structural morphologies, but also across a diverse range of biomedical and healthcare applications. These include drug and vaccine delivery, biosignal acquisition, point-of-care diagnostics, and minimally invasive fluid collection. Microneedles have emerged as innovative, patient-friendly devices offering distinct advantages such as minimal invasiveness, portability, precision, and high efficiency. However, the success of a microneedle system largely depends on three critical aspects: material selection, microneedle geometry, and the fabrication technique employed.

This review offers a comprehensive framework for the rational design of microneedle systems. It emphasizes that for any targeted application, it is essential to clearly define the clinical or diagnostic need and then tailor the MN design accordingly. Key design parameters- such as needle length, tip diameter, aspect ratio, array density, material biocompatibility, and fabrication method- must be carefully optimized to ensure maximum therapeutic or diagnostic efficacy while maintaining patient comfort and safety. As microneedle technology continues to evolve, interdisciplinary approaches combining materials science, mechanical engineering, and biomedical innovation will be crucial to advance the next generation of customized, scalable, and multifunctional MN systems for widespread clinical translation.

References

1. Gao, Z., Zhang, J., Liu, G.-F., & Ji, L.-X. (2021). Research trends from 2010 to 2020 for pain treatment with acupuncture: A bibliometric analysis. Journal of Pain Research.

2. Weiss, S. C. (2011). Conventional topical delivery systems. Dermatologic Therapy, 24(5), 471–476.

3. Waghule, T., Singhvi, G., Dubey, S., Kumar, M., Pandey, M. M., & Gupta, M. (2019). Microneedle: A smart approach and increasing potential for transdermal drug delivery system. Biomedicine & Pharmacotherapy, 109, 1249–1258.

4. Amarnani, R., & Shende, P. (2022). Microneedles in diagnostic, treatment and theranostics: An advancement in minimally-invasive delivery system. Biomedical Microdevices, 24, Article 5.

5. Jung, J. H., & Jin, S. G. (2021). Microneedle for transdermal drug delivery: Current trends and fabrication. Journal of Pharmaceutical Investigation, 51, 503–517.

6. Kidd, B. L., Langford, R. M., & Wodehouse, T. (2007). Current approaches in the treatment of arthritic pain. Arthritis Research & Therapy, 9(3), 1–7. https://doi.org/10.1186/ar2183

7. Russell, R. I. (2001). Non-steroidal anti-inflammatory drugs and gastrointestinal damage—Problems and solutions. Postgraduate Medical Journal, 77(904), 82–88.

8. Centers for Disease Control and Prevention. (n.d.). Parenteral administration of ivermectin in a patient with disseminated strongyloidiasis. PubMed. Retrieved from

9. Hou, L., Fan, C., Liu, C., Qu, Q., Wang, C., & Shi, Y. (2018). Evaluation of repeated exposure systemic toxicity test of PVC with new plasticizer on rats via dual parenteral routes. Regenerative Biomaterials, 5(1), 9–16.

10. Hu, W., Bian, Q., Zhou, Y., & Gao, J. (2022). Pain management with transdermal drug administration: A review. International Journal of Pharmaceutics, 618, 121696.

11. Leppert, W., Malec-Milewska, M., Zajaczkowska, R., & Wordliczek, J. (2018). Transdermal and topical drug administration in the treatment of pain. Molecules: A Journal of Synthetic Chemistry and Natural Product Chemistry, 23(7).

12. Gorantla, S., Batra, U., Puppala, E. R., Waghule, T., Naidu, V. G. M., & Singhvi, G. (2022). Emerging trends in microneedle-based drug delivery strategies for the treatment of rheumatoid arthritis. Expert Opinion on Drug Delivery, 19(3), 395–407.

13. Rizwan, M., Aqil, M., Talegaonkar, S., Azeem, A., Sultana, Y., & Ali, A. (2009). Enhanced transdermal drug delivery techniques: An extensive review of patents. Recent Patents on Drug Delivery & Formulation, 3(2), 105–124.

14. Bariya, S. H., Gohel, M. C., Mehta, T. A., & Sharma, O. P. (2012). Microneedles: An emerging transdermal drug delivery system. Journal of Pharmacy and Pharmacology, 64(1), 11–29.

15. Dabholkar, N., Gorantla, S., Waghule, T., Rapalli, V. K., Kothuru, A., Goel, S., & Singhvi, G. (2021). Biodegradable microneedles fabricated with carbohydrates and proteins: Revolutionary approach for transdermal drug delivery. International Journal of Biological Macromolecules, 170, 602–621.

16. Vandervoort, J., & Ludwig, A. (2008). Microneedles for transdermal drug delivery: A minireview. Drug Development and Industrial Pharmacy, 34(12), 1285–1298.

17. Gorantla, S., Dabholkar, N., Sharma, S., Rapalli, V. K., Alexander, A., & Singhvi, G. (2021). Chitosan-based microneedles as a potential platform for drug delivery through the skin: Trends and regulatory aspects. International Journal of Biological Macromolecules, 184, 438–453.

18. Amodwala, S., Kumar, P., & Thakkar, H. P. (2017). Statistically optimized fast dissolving microneedle transdermal patch of meloxicam: A patient-friendly approach to manage arthritis. European Journal of Pharmaceutical Sciences, 104, 114–123.

19. Bariya, S. H., Gohel, M. C., Mehta, T. A., & Sharma, O. P. (2012). Microneedles: An emerging transdermal drug delivery system. Journal of Pharmacy and Pharmacology, 64(1), 11–29.

20. Zhang, Q., Xu, C., Lin, S., Zhou, H., Yao, G., & Liu, H. (2018). Synergistic immune reaction of acupuncture-like dissolving microneedles containing hymopentin at acupoints in immune-suppressed rats. Acta Pharmaceutica Sinica B, 8(3), 449–457.

21. Prausnitz, M. R., & Langer, R. (2008). Transdermal drug delivery. Nature Biotechnology, 26(11), 1261–1268.

22. Waghule, T., Singhvi, G., Dubey, S. K., Pandey, M. M., Gupta, G., Singh, M., & Dua, K. (2019). Microneedle: A smart approach and increasing potential for transdermal drug delivery system. Biomedicine & Pharmacotherapy, 109, 1249–1258.

23. Williams, A. C., & Barry, B. W. (2004). Penetration enhancers. Advanced Drug Delivery Reviews, 56(5), 603–618.

24. Singh, A., & Yadav, S. (2016). Microneedling: Advances and widening horizons. Indian Dermatology Online Journal, 7(4), 244–254.

25. Mikszta, J. A., Alarcon, J. B., Brittingham, J. M., Sutter, D. E., Pettis, R. J., & Harvey, N. G. (2002). Improved immune responses with microneedle-based vaccine delivery. Clinical and Vaccine Immunology, 9(5), 415–419.

26. Martanto, W., Davis, S. P., Holiday, N. R., Wang, J., Gill, H. S., & Prausnitz, M. R. (2004). Transdermal delivery of insulin using microneedles in vivo. Pharmaceutical Research, 21, 947–952.

27. Cheung, K., & Das, D. (2014). Microneedles for drug delivery: Trends and progress. Drug Delivery, 21(5), 2338–2354.

28. Niu, L., Chu, L. Y., Burton, S. A., Hansen, K. J., & Panyam, J. (2019). Stimuli-responsive polymeric prodrug-based nanomedicine delivering nifuroxazide and doxorubicin against primary breast cancer and pulmonary metastasis. Journal of Controlled Release, 294, 268–278.

29. Dillon, C., Hughes, H., O’Reilly, N. J., & McLaughlin, P. (2017). Design and evaluation of dissolving microneedles for transdermal delivery of naloxone. International Journal of Pharmaceutics, 526(1–2), 125–136.

30. Zhu, J., Dong, L., Du, H., Mao, J., Xie, Y., Wang, H., & Lan, J. (2019). 5‐Aminolevulinic acid‐loaded hyaluronic acid dissolving microneedles for effective photodynamic therapy of superficial tumors with enhanced long‐term stability. Advanced Healthcare Materials, 8(20), 1900209.

31. Akhtar, N. (2014). Microneedles: An innovative approach to transdermal delivery. International Journal of Pharmacy and Pharmaceutical Sciences, 6(4), 18–25.

32. Oliveira, C., Teixeira, J. A., Oliveira, N., Ferreira, S., & Botelho, C. M. (2024). Microneedles’ device: Design, fabrication, and applications. Macromol, 4(2), 320–355.

33. Bariya, S. H., Gohel, M. C., Mehta, T. A., & Sharma, O. P. (2012). Microneedles: An emerging transdermal drug delivery system. Journal of Pharmacy and Pharmacology, 64, 11–29.

34. Lee, J. W., & Prausnitz, M. R. (2018). Drug delivery using microneedle patches: Not just for skin. Expert Opinion on Drug Delivery, 15(6), 541–543.

35. Zhao, Z., Chen, Y., & Shi, Y. (2020). Microneedles: A potential strategy in transdermal delivery and application in the management of psoriasis. RSC Advances, 10, 15073–15085.

36. Kim, Y. C., Park, J. H., & Prausnitz, M. R. (2012). Microneedles for drug and vaccine delivery. Advanced Drug Delivery Reviews, 64(14), 1547–1568.

37. Cheung, K., & Das, D. (2014). Microneedles for drug delivery: Trends and progress. Drug Delivery, 21(5), 2338–2354.

38. Priya, S., & Singhvi, G. (2022). Microneedles-based drug delivery strategies: A breakthrough approach for the management of pain. Biomedicine & Pharmacotherapy, 155, 113751.

39. Guttman-Yassky, E., Hanifin, J. M., Boguniewicz, M., Wollenberg, A., Bissonnette, R., Purohit, V., Kilty, I., Tallman, A. M., & Zielinski, M. A. (2019). The role of phosphodiesterase 4 in the pathophysiology of atopic dermatitis and the perspective for its inhibition. Experimental Dermatology, 28(1), 3–10.

40. Aksit, A., Arteaga, D. N., Arriaga, M., Wang, X., Watanabe, H., Kasza, K. E., Lalwani, A. K., & Kysar, J. W. (2018). In-vitro perforation of the round window membrane via direct 3D printed microneedles. Biomedical Microdevices, 20, 47.

41. Yadav, V., Sharma, P. K., Murty, U. S., Mohan, N. H., Thomas, R., Dwivedy, S. K., & Banerjee, S. (2021). 3D printed hollow microneedles array using stereolithography for efficient transdermal delivery of rifampicin. International Journal of Pharmaceutics, 605, 120815.

42. Vinayakumar, K. B., Silva, M. D., Martins, A., Mundy, S., González-Losada, P., & Sillankorva, S. (2023). Levofloxacin-loaded microneedles produced using 3D-printed molds for Klebsiella pneumoniae biofilm control. Advanced Therapeutics, 6(1), 2200320.

43. Bora, P., Kumar, L., & Bansal, A. (2008). Microneedle technology for advanced drug delivery. Evolving Vistas in Drug Delivery.

44. Li, J., Zeng, M., Shan, H., & Tong, C. (2017). Microneedle patches as drug and vaccine delivery platform. Current Medicinal Chemistry, 24(22), 2413–2422.

45. Singh, A., & Yadav, S. (2016). Microneedling: Advances and widening horizons. Indian Dermatology Online Journal, 7(4), 244–254.

46. Alimardani, V., Abolmaali, S. S., Yousefi, G., Rahiminezhad, Z., Abedi, M., Tamaddon, A., & Ahadian, S. (2021). Microneedle arrays combined with nanomedicine approaches for transdermal delivery of therapeutics. Journal of Clinical Medicine, 10(18), 4037.

47. Indermun, S., Luttge, R., Choonara, Y. E., Kumar, P., Du Toit, L. C., Modi, G., & Pillay, V. (2014). Current advances in the fabrication of microneedles for transdermal delivery. Journal of Controlled Release, 185, 130–138.

48. Gupta, J., Gupta, R., & Vanshita. (2021). Microneedle technology: An insight into recent advancements and future trends in drug and vaccine delivery. Assay and Drug Development Technologies, 19(2), 97–114.

49. Kawre, S., Suryavanshi, P., Lalchandani, D. S., Deka, M. K., Porwal, P. K., Kaity, S., Roy, S., & Banerjee, S. (2024). Bioinspired labrum-shaped stereolithography (SLA) assisted 3D printed hollow microneedles (HMNs) for effectual delivery of ceftriaxone sodium. European Polymer Journal, 204, 112702.

50. Anjani, Q. K., Permana, A. D., Cárcamo-Martínez, Á., Domínguez-Robles, J., Tekko, I. A., Larrañeta, E., Vora, L. K., Ramadon, D., & Donnelly, R. F. (2021). Versatility of hydrogel-forming microneedles in in vitro transdermal delivery of tuberculosis drugs. European Journal of Pharmaceutics and Biopharmaceutics, 158, 294–312.