Microneedles: An Approach in Transcutaneous Drug Delivery: A Review

Abstract

Transcutaneous drug delivery carried out a carner in the conveying of drugs to get direct acces across the scin deep into the systemic circulation. Transcutaneous drug delivery has a number of benefits including impoved patient compliance, sustained release, dealy of gastric irritation, as well as elimination of pre-systemic first-pass eflect. It gives attraction to many researchers due to various conventional medicine ben fits. Due to the strong matches of pral drug delivery systern and the pain related with the use of needles case of injections, drug delivery research has greatly adjusted towards the transderntal route. Delivery of drugs via transcutaneous route has proved to be the convenient route for various dinical implications in this review, we tell about different types of microneedles are described and its methods of assemble. Microneedles can be fabricated in different forms like dedicate, solid, and dissolving. There are also hydrogel forming microneedles in relation of hydrogel forming microneedles, special attention, these are inevativemicroneedles which does not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Regulatory give the go ahead approved several microneedles for clinical uses are also examined. The last part of this review discusses concerns and challenges about microneedles use

Introduction

Overview

The skin is the body's largest organ and acts as a barrier against harmful substances and water loss. However, its structure—especially the stratum corneum—makes drug delivery through the skin challenging. Transcutaneous drug delivery (TDD) systems aim to administer therapeutic agents through the skin into systemic circulation in a controlled, non-invasive manner.

Advantages of TDD

1. Avoids liver metabolism (first-pass effect).

2. Maintains steady drug levels.

3. Requires lower doses.

4. Fewer side effects, especially gastrointestinal.

5. Easy to discontinue in case of adverse reactions.

6. Ideal for unconscious or non-cooperative patients.

7. Enhances patient compliance.

Disadvantages of TDD

1. Only drugs with certain physical/chemical properties can penetrate the skin.

2. Not effective for high-dosage drugs (>25 mg/day).

3. Can cause skin irritation.

4. Limited to specific clinical needs.

5. Skin permeability varies between individuals.

6. Large or charged molecules cannot pass through skin easily.

7. Cannot provide pulsatile (on/off) drug release.

Microneedles: A TDD Innovation

Microneedles (MNs) are micro-scale needles (1–1500 µm long) arranged on patches to painlessly penetrate the skin, enhancing drug delivery. They offer a promising solution for delivering both small and large molecules.

Types of Microneedles:

1. Hollow MNs: Deliver liquid drugs through tiny tubes.

2. Solid MNs: Create microchannels in the skin; drug is applied afterward.

3. Dissolving MNs: Made from biodegradable polymers; dissolve after insertion, releasing drugs.

4. Coated MNs: Drugs are coated on the needle surface and released on skin contact.

5. Hydrogel-forming MNs: Swell upon skin insertion to enable sustained drug release.

Key Features of Microneedles:

• Minimal pain (compared to hypodermic needles).

• Vary in size, shape, and material (silicon, metal, polymer).

• Deliver drugs in a controlled, targeted manner.

• Must be strong enough to penetrate skin without breaking.

Fabrication Techniques

Microneedles are made using micro-electromechanical systems (MEMS) involving:

• Deposition (creating thin layers),

• Patterning (using photolithography or similar),

• Etching (removing material to shape the microneedles).

Materials include silicon, stainless steel, biodegradable polymers, and newer hydrogel composites.

Evaluation of Microneedles

In Vitro Testing

• Conducted in gels (agarose/methanol) or cadaver skin.

• Measures penetration depth, bending strength, drug delivery rate, and dissolution time.

In Vivo Testing

• Performed on animals (mice, rabbits, guinea pigs).

• Evaluates safety, toxicity, immune response, and delivery efficacy.

Marketed Microneedle Products & Clinical Trials

• Intanza/IDflu: Approved influenza vaccine using microneedles.

• ZP-PTH: A microneedle-based product for osteoporosis in clinical trials.

• Microneedles are also being developed for cosmetics, biologic drugs, and vaccines.

Conclusion

Microneedles, whether utilized as patches or arrays, have emerged as promising vehicles for the efficient transdermal administration of various macromolecular medications. Numerous research studies have validated that microneedles can serve as effective carriers to enhance permeation into systemic circulation, offering a painless, efficient, and safe method for drug delivery. In the future, microneedles are expected to play a significant role in the development and design of controlled drug delivery systems for a range of medications. These pain-free systems are gradually gaining recognition and are likely to become key devices for controlled drug release going forward. Consequently, it is concluded that these systems represent an effective and superior option compared to traditional needle-based formulations for transdermal delivery.

References

[1] Dhamecha DL, Rathi AA, Saifee M, Lahoti SR, Dehghan MHG. Drug vehicle based approaches of penetration enhancement. Int J Pharm PharmaSci 2009; 1(1): 24-26 [2] NidaAkhtar, Microneedles: An Innovative Approach to Transdermal Delivery. International journal of pharmacy and pharmaceutical sciences. Vol.6 issue 4,2014: 18-25 [3] Ranade VV. Drug delivery systems: transdermal drug delivery. J ClinPharmacol 1991; 31(5): 401-418. [4] Lhernould M.S., Deleers M., Delchambre A. Hollow polymer microneedles array resistance and insertion tests, Int. J. Pharm. 2015; 480:152-157. doi:10.1016/j.ijpharm.2015.01.019 [5] Sharma N, Bharat PS, Mahajan U. Blooming pharmaindystry with transdermal drug delivery system. IndoGlobal J Pharm Sci 2012; 2(3): 262-278 [6] Rani 5, Saroha K, Syan N, Mathur P. Transdermal patches a successful tool in transdermal drug delivery system: an overview , Der Pharmacia Sinca 2011;2(5):17-29 [7] Arunachalam A, Karthikeyan M, Kumar M, Prathap M, Sethuraman S, Kumar SA, Manidipa S. Transdermal drug delivery system: a review. Curr Pharm Res 2010; 1(1): 70-81. [8] Ehdaie B. Enhanced delivery of transdermal drugs through human skin with novel carriers. J Pharm Biomed Sci 2011;1(8): 161-166 [9] Prausnitz MR, Langer R. Transdermal Drug delivery. Nature Biotechnol 2008; 26: 1261-1268. [10] Patel D, Chaudhary SA, Parmar B, Bhura N. Transdermal drug delivery system: a review. Pharm Innov 2012, 1(4): 66-75. [11] Lhernould M.S., Deleers M., Delchambre A. Hollow polymer microneedles array resistance and insertion tests. Int. J. Pharm. 2015;480:152-157. doi: 10.1016/j.ijpharm.2015.01.019. [12] Andrews S.N., Jeong E., Prausnitz M.R. Transdermal delivery of molecules is limited by full epidermis, not just stratum corneum. Pharm. Res. 2013;30:1099-1109. doi: 10.1007/s11095-012-0946-7. [13] Jepps O.G., Dancik Y., Anissimov Y.G., Roberts M.S. Modeling the human skin barrier-Towards a better understanding of dermal absorption. Adv. Drug Deliv. Rev. 2013;65:152-168. doi: 10.1016/j.addr.2012.04.003. [14] Olatunji O., Das D.B., Garland MJ., Belaid L., Donnelly R.F. Influence of array interspacing on the force required for successful microneedle skin penetration: Theoretical and practical approaches. J. Pharm. Sci. 2013;102:1209-1221. doi: 10.1002/jps.23439. [15] Cheung K., Han T., Das D.B. Effect of Force of Microneedle Insertion on the Permeability of Insulin in Skin. J. Diabetes Sci. Technol. 2014;8:444-452. doi: 10.1177/1932296813519720. [16] Kim Y.C., Park J.H., Prausnitz M.R. Microneedles for drug and vaccine delivery. Adv. Drug Deliv. Rev.2012;64:1547-1568. doi: 10.1016/j.addr.2012.04.005. [17] Verbaan F.J., Bal S.M., van den Berg D.J., Dijksman J.A., van Hecke M., Verpoorten H., van den Berg A., Luttge R., Bouwstra J.A. Improved piercing of microneedle arrays in dermatomed human skin by an impact insertion.method. J. Control. Release. 2008;128:80-88. doi: 10.1016/j.jconrel.2008.02.009. [18] Vinayakumar K.B., Hegde G.M., Nayak M.M., Dinesh N.S., Rajanna K. Fabrication and characterization of gold coated hollow silicon microneedle array for drug delivery. Microelectron. Eng. 2014;128:12-18. doi: 10.1016/j.mee.2014.05.039. [19] Gupta J., Gill H.S., Andrews S.N., Prausnitz M.R. Kinetics of skin resealing after insertion of microneedles inhuman subjects. J. Control. Release. 2011;154:148-155. doi: 10.1016/j.jconrel.2011.05.021 [20] Henry S., McAllister D.V., Allen M.G., Prausnitz M.R. Microfabricatedmicroneedles: A novel approach totransdemal drug delivery. J. Pharm, Sci. 1998:87:922-925. doi: 10.1021/js980042+. [21] Wang Q., Yao G., Dong P., Gong Z., Li G., Zhang K., Wu C. Investigation on fabrication process of dissolving microneedle arrays to improve effective needle drug distribution. Eur. J. Pharm. Sci. 2015;66:148-156. doi: 10.1016/j.ejps.2014.09.011 [22] Sullivan S.P., Koutsonanos D.G., del Pilar Martin M., Lee J.W., Zarnitsyn V., Choi S.-O., Murthy N., Compans R.W., Skountzou I., Prausnitz M.R. Dissolving polymer microneedle patches for influenza vaccination. Nat. Med. 2010;16:915-920. doi: 10.1038/nm.2182. [23] Hong X., Wei L., Wu F., Wu Z., Chen L., Liu Z., Yuan W. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine. Drug Des. Dev. Ther. 2013:945-952 [24] Chen M.-C., Huang 5.-F., Lai K.-Y., Ling M.-H. Fully embeddable chitosan microneedles as a sustained release depot for intradermal vaccination. Biomaterials. 2013,34:3077-3086. doi: 10.1016/j.biomaterials.2012.12.041. [25] Pearton M., Saller V., Coulman 5.A., Gateley C., Anstey A.V., Zarnitsyn V., Birchall J.C. Microneedle delivery of plasmid DNA to living human skin: Formulation coating, skin insertion and gene expression. J. Control. Release. 2012;160:561-569. doi: 10.1016/j.jconrel.2012.04.005. [26] Khan H., Mehta P., Msallam H., Armitage D., Ahmad Z. Smart microneedle coatings for controlled delivery. and biomedical analysis. J. Drug Target. 2014:22:790-795. doi: 10.3109/1051186X.2014.921926. [27] Ma Y., Gill H.5. Coating solid dispersions on microneedles via a molten dip-coating method: development and in vitro evaluation for transdermal delivery of a water-insoluble drug. J. Pharm. Sci. 2014;103:3621-3630. doi 10.1002/jps.24159. [28] Donnelly R.F., Raj Singh T.R., Alkilani A.Z., McCrudden M.T.C., O\'Neill S., O\'Mahony C., Armstrong K., Mcloone N., Kole P., Woollson A.D. Hydrogel-forming microneedle arrays exhibit antimicrobial properties: Potential for enhanced patient safety. Int. J. Pharm. 2013;451:76-91. doi: 10.1016/j.ijpharm.2013.04.045. [29] Chen B, Wei J, Tay FEH, Wong YT, Iliescu C. Silicon micro needles array biodegradable tips for transdermal drug delivery. DTIP MemsMoems 2007, 1: 25-27 [30] Sheer A, Chauhan M. Ethosomes as vesicular carrier for enhanced transdermal delivery of ketoconazole-formulation and evaluation. IJPI\'s J Pharm Cosmetol 2011, 1(3): 1-14. [31] Alvarez-Figueroa M, Delgado-Charro M. Passive and iontophoretic transdermal penetration of methotrexate Int J Pharm 2001; 212: 101-107. [32] Nolan LMA, Corish J, Corrigan Ol, Fitzpatrick D. Iontophoretic and chemical enhancement of drug delivery: Part-1: Across Artificial Membranes. Int J Pharm 2003; 257: 41-55. [33] Bendas ER, Tadros MI. Enhanced transdermal delivery of salbutamol sulphate via ethosomes. AAPS PharmSciTech 2007, 8: 1-15. [34] Saroha K, Nanda S, Rani S. Chemical penetration enhances: a novel approach in transdermal drug delivery system. Int 1 Curr Pharm Res 2011; 3(4): 5-9. [35] Kumar AV, Kulkarni PR, Raut RA. Microneedles: promising technique for transdermal drug delivery. IntIPharm Bio Sci 2011; 2(1): 684-708. [36] Tabassum N, Sofi A, Khuroo T. Microneedle technology: a new drug delivery system. Int 1 Res Pharm Biomed Sci 2011: 2(1): 59-62. [37] Srinivas P, Shanthi CL, Sadanandam MS. Miconeedles patches in drug delivery: a review. Int J Pharm Tech 2010; 2(3): 329-344. [38] Vandervoort J, Ludig A. Microneedles for transdermal drug delivery: a minireview. Front Riasci 2008; 1(13): 1711-1715. [39] Yadav JD. Microneedles: promising technique for transdermaldrug delivery. Int J Pharm BioSci 2011; 2(1): 684-708. [40] Paik SJ, Lim JM, Jung I, Park Y, Byun S, Chung S. A novel microneedle array integrated with a PDMS biochip for micro fluid system. Transducers Solid-State Sensors Actuators Microsys 2003; 2: 1446-1449.

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Copyright © 2025 Rahul Shinde , Atish Kore, Ashish Kadam, Ganesh More, Kunal Jagtap. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.