ABSTRACT:
Diabetes management requires frequent administration of peptide therapeutics such as insulin and glucagon-like peptide-1 (GLP-1) receptor agonists, which are currently delivered almost exclusively via subcutaneous injections. Despite their efficacy, injections are associated with pain, needle phobia, injection-site reactions, lipohypertrophy, and poor patient adherence. Transdermal delivery using microneedle arrays and advanced patches has emerged as a promising minimally invasive alternative that can bypass the stratum corneum barrier while improving patient comfort and compliance. This review comprehensively examines the design, fabrication, and application of microneedle arrays (dissolving, coated, hollow, and hydrogel-forming) and transdermal patches for the delivery of peptides in diabetes. Particular focus is placed on skin penetration strategies, including chemical enhancers, physical assistance techniques, and nanotechnology integration, along with material selection, drug loading, and controlled release mechanisms. The pharmacokinetic performance, bioavailability, and safety profiles of these systems are critically compared with conventional subcutaneous injections. Furthermore, this review highlights patient-centric advantages, including reduced pain, improved adherence, dose flexibility, and better quality of life. Current challenges in regulatory approval, long-term stability, manufacturing scale-up, and clinical translation are discussed. Emerging trends such as smart, stimuli-responsive, and closed-loop microneedle systems are also explored as future directions for precision diabetes care.
Cite this article:
Waghamare Suresh. Microneedle Arrays and Transdermal Patches for Peptide Delivery in Diabetes: Design, Skin Penetration Strategies, and Patient-Centric Advantages over Subcutaneous Injections. Research Journal of Pharmaceutical Dosage Forms and Technology.2026; 18(3):255-4. doi: 10.52711/0975-4377.2026.00037
Cite(Electronic):
Waghamare Suresh. Microneedle Arrays and Transdermal Patches for Peptide Delivery in Diabetes: Design, Skin Penetration Strategies, and Patient-Centric Advantages over Subcutaneous Injections. Research Journal of Pharmaceutical Dosage Forms and Technology.2026; 18(3):255-4. doi: 10.52711/0975-4377.2026.00037 Available on: https://www.rjpdft.com/AbstractView.aspx?PID=2026-18-3-12
11. REFERENCE:
1. Genitsaridi I, Salpea P, Salim A, Sajjadi SF, Tomic D, James S, et al. 11th edition of the IDF Diabetes Atlas: global, regional, and national diabetes prevalence estimates for 2024 and projections for 2050. Lancet Diabetes Endocrinol 2026; 14: 149–56. https://doi.org/10.1016/S2213-8587(25)00299-2.
2. Zhang Y, Yu J, Kahkoska AR, Wang J, Buse JB, Gu Z. Advances in transdermal insulin delivery. Adv Drug Deliv Rev 2019; 139: 51–70. https://doi.org/10.1016/j.addr.2018.12.006.
3. Chen G, Yu J, Gu Z. Glucose-Responsive Microneedle Patches for Diabetes Treatment. J Diabetes Sci Technol 2019; 13: 41–8. https://doi.org/10.1177/1932296818778607.
4. Ng LC, Gupta M. Transdermal drug delivery systems in diabetes management: A review. Asian J Pharm Sci 2020; 15: 13–25. https://doi.org/10.1016/j.ajps.2019.04.006.
5. Mauldin EA, Peters-Kennedy J. Integumentary System. Jubb Kennedy Palmers Pathol. Domest. Anim. Vol. 1, Elsevier; 2016, p. 509-736.e1. https://doi.org/10.1016/B978-0-7020-5317-7.00006-0.
6. Raina N, Rani R, Thakur VK, Gupta M. New Insights in Topical Drug Delivery for Skin Disorders: From a Nanotechnological Perspective. ACS Omega 2023; 8: 19145–67. https://doi.org/10.1021/acsomega.2c08016.
7. Hong Y, Yu H, Wang L, Chen X, Huang Y, Yang J, et al. Transdermal Insulin Delivery and Microneedles-based Minimally Invasive DeliverySystems. Curr Pharm Des 2022; 28: 3175–93. https://doi.org/10.2174/1381612828666220608130056.
8. Alkilani A, McCrudden MT, Donnelly R. Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the Stratum Corneum. Pharmaceutics 2015; 7: 438–70. https://doi.org/10.3390/pharmaceutics7040438.
9. Shah SWA, Li X, Yuan H, Shen H, Quan S, Pan G, et al. Innovative transdermal drug delivery systems: Benefits, challenges, and emerging application. BMEMat 2025; 3: e70001. https://doi.org/10.1002/bmm2.70001.
10. Trommer H, Neubert RHH. Overcoming the Stratum Corneum: The Modulation of Skin Penetration. Skin Pharmacol Physiol 2006; 19: 106–21. https://doi.org/10.1159/000091978.
11. Bhavsar J, Kasture K, Salvi BV, Shende P. Strategies for transportation of peptides across the skin for treatment of multiple diseases. Ther Deliv 2025; 16: 63–86. https://doi.org/10.1080/20415990.2024.2411943.
12. U. Waghmare S, R. Kudhekar A, H. Sayyad J, B. Yadav D. Enhanced delivery through modified xanthan gum in solid dispersions. Indian Drugs 2026; 63: 29–34. https://doi.org/10.53879/id.63.04.15163.
13. Gattu K, Godugu D, Jain H, Jadhav K, Cho H, Rojekar S. Microneedle Technologies for Drug Delivery: Innovations, Applications, and Commercial Challenges. Micromachines 2026; 17: 102. https://doi.org/10.3390/mi17010102.
14. Moawad F, Pouliot R, Brambilla D. Dissolving microneedles in transdermal drug delivery: A critical analysis of limitations and translation challenges. J Controlled Release 2025; 383: 113794. https://doi.org/10.1016/j.jconrel.2025.113794.
15. Suresh W, Kudhekar A. Healing by Design: Bioactive Hydrogels as Intelligent Tissue Architects. Asian J Pharm Technol 2025: 377–84. https://doi.org/10.52711/2231-5713.2025.00056.
16. Aldawood FK, Andar A, Desai S. A Comprehensive Review of Microneedles: Types, Materials, Processes, Characterizations and Applications. Polymers 2021; 13: 2815. https://doi.org/10.3390/polym13162815.
17. Kim Y-C, Park J-H, Prausnitz MR. Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev 2012; 64: 1547–68. https://doi.org/10.1016/j.addr.2012.04.005.
18. Oliveira C, Teixeira JA, Oliveira N, Ferreira S, Botelho CM. Microneedles’ Device: Design, Fabrication, and Applications. Macromol 2024; 4: 320–55. https://doi.org/10.3390/macromol4020019.
19. Sen O, Poddar P, Sarkar P, Das S, Manna S. Current advancements in microneedle technology for therapeutic and biomedical applications. Sens Int 2025; 6: 100325. https://doi.org/10.1016/j.sintl.2024.100325.
20. Tucak A, Sirbubalo M, Hindija L, Rahić O, Hadžiabdić J, Muhamedagić K, et al. Microneedles: Characteristics, Materials, Production Methods and Commercial Development. Micromachines 2020;11:961. https://doi.org/10.3390/mi11110961.
21. Ando D, Miyatsuji M, Sakoda H, Yamamoto E, Miyazaki T, Koide T, et al. Mechanical Characterization of Dissolving Microneedles: Factors Affecting Physical Strength of Needles. Pharmaceutics 2024; 16: 200. https://doi.org/10.3390/pharmaceutics16020200.
22. Guillot AJ, Cordeiro AS, Donnelly RF, Montesinos MC, Garrigues TM, Melero A. Microneedle-Based Delivery: An Overview of Current Applications and Trends. Pharmaceutics 2020; 12: 569. https://doi.org/10.3390/pharmaceutics12060569.
23. Takehara H, Inada M, Kanda Y, Ichiki T. Mechanical finite element analysis of needle tip shape to develop insertable polymer-based microneedle without plastic deformation. J Mech Behav Biomed Mater 2025; 163: 106885. https://doi.org/10.1016/j.jmbbm.2025.106885.
24. Avcil M, Çelik A. Microneedles in Drug Delivery: Progress and Challenges. Micromachines 2021; 12: 1321. https://doi.org/10.3390/mi12111321.
25. Al-Remawi M, Jaber N, Elsayed A, Alsafadi D, Salah KA. Stabilization of insulin using low molecular weight chitosan carbonate nanocarrier. Carbohydr Polym 2022; 291: 119579. https://doi.org/10.1016/j.carbpol.2022.119579.
26. Yenurkar D, Shrivastava A, Mandal S, Kumar V, Pradhan L, Tripathi S, et al. Development of Emodin Nanocrystal‐Loaded Hydrogel Patch for Rapid Wound Repair. Macromol Biosci 2026;26:e00581. https://doi.org/10.1002/mabi.202500581.
27. Zhao J, Xu G, Yao X, Zhou H, Lyu B, Pei S, et al. Microneedle-based insulin transdermal delivery system: current status and translation challenges. Drug Deliv Transl Res 2022; 12: 2403–27. https://doi.org/10.1007/s13346-021-01077-3.
28. Fan L, Huang J, Ma S. Recent advances in delivery of transdermal nutrients: A review. Exp Dermatol 2024; 33: e14966. https://doi.org/10.1111/exd.14966.
29. Pan X, Zhong Z, Hu X, Wu J, Huang W, Li W, et al. Application of nanotechnology in anti-aging cosmetics: advantages, challenges, and prospects. Polym Bull 2025; 82 :8635–725. https://doi.org/10.1007/s00289-025-05903-3.
30. Kumar A, Kumar D, Kondaveeti SB, Shiekmydeen J, Awasthi A, Singh TG, et al. Polysaccharide-based microneedles for advanced wound healing: recent advances and future challenges. Int J Pharm 2025; 685: 126-256. https://doi.org/10.1016/j.ijpharm.2025.126256.
31. Van Der Maaden K, Sekerdag E, Jiskoot W, Bouwstra J. Impact-Insertion Applicator Improves Reliability of Skin Penetration by Solid Microneedle Arrays. AAPS J 2014;16:681–4. https://doi.org/10.1208/s12248-014-9606-7.
32. Zhang N, Zhou X, Liu L, Zhao L, Xie H, Yang Z. Dissolving Polymer Microneedles for Transdermal Delivery of Insulin. Front Pharmacol 2021;12:719905. https://doi.org/10.3389/fphar.2021.719905.
33. Sun T, Dasgupta A, Zhao Z, Nurunnabi M, Mitragotri S. Physical triggering strategies for drug delivery. Adv Drug Deliv Rev 2020;158:36–62. https://doi.org/10.1016/j.addr.2020.06.010.
34. Tari K, Khamoushian S, Madrakian T, Afkhami A, Łos MJ, Ghoorchian A, et al. Controlled Transdermal Iontophoresis of Insulin from Water-Soluble Polypyrrole Nanoparticles: An In Vitro Study. Int J Mol Sci 2021;22:12479. https://doi.org/10.3390/ijms222212479.
35. Opatha SAT, Titapiwatanakun V, Chutoprapat R. Transfersomes: A Promising Nanoencapsulation Technique for Transdermal Drug Delivery. Pharmaceutics 2020; 12:855. https://doi.org/10.3390/pharmaceutics12090855.
36. S.U W, Mishra A, S.G K. Recent Advances in Polymeric Microparticles - Based Drug Delivery Systems for the Treatment of Diabetes. Res J Pharm Technol 2025: 1611–8. https://doi.org/10.52711/0974-360X.2025.00231.
37. Serrano DR, Juste F, Anaya BJ, Ramirez BI, Sánchez-Guirales SA, Quispillo JM, et al. Exosome-Based Drug Delivery: A Next-Generation Platform for Cancer, Infection, Neurological and Immunological Diseases, Gene Therapy and Regenerative Medicine. Pharmaceutics 2025; 17: 1336. https://doi.org/10.3390/pharmaceutics17101336.
38. Wu C, Zong Z, Hua F, Wu J, Shen Y, Tian Y, et al. Advances in Microneedle Drug Delivery for Obesity: Mechanisms, Applications, and Perspectives. Int J Nanomedicine. 2025; 20: 15213–34. https://doi.org/10.2147/IJN.S566132.
39. Shelke PS, U W, Rk S, Pawar TB, Bhingar HR, Narode PA. A review on solubility enhancement technique. Int J Pharm Pharm Sci 2024; 6:144–8. https://doi.org/10.33545/26647222.2024.v6.i1b.113.
40. Mdanda S, Ubanako P, Kondiah PPD, Kumar P, Choonara YE. Recent Advances in Microneedle Platforms for Transdermal Drug Delivery Technologies. Polymers. 2021; 13: 2405. https://doi.org/10.3390/polym13152405.
41. Sasaki GH. The Significance of Trans-Epidermal Water Loss After Microneedling and Microneedling-Radiofrequency Procedures: Histological and IRB-Approved Safety Study. Aesthetic Surg J Open Forum. 2019; 1: ojz017. https://doi.org/10.1093/asjof/ojz017.
42. Liu Q, Ranallo R, Rios C, Grice EA, Moon K, Gallo RL. Crosstalk between skin microbiota and immune system in health and disease. Nat Immunol. 2023; 24: 895–8. https://doi.org/10.1038/s41590-023-01500-6.
43. Zhang E, Zhu H, Song B, Shi Y, Cao Z. Recent advances in oral insulin delivery technologies. J Controlled Release. 2024; 366: 221–30. https://doi.org/10.1016/j.jconrel.2023.12.045.
44. Alsbrooks K, Hoerauf K. Prevalence, causes, impacts, and management of needle phobia: An international survey of a general adult population. PLOS ONE. 2022; 17: e0276814. https://doi.org/10.1371/journal.pone.0276814.
45. Isaacs DM, Kruger DF, Spollett GR. Optimizing Therapeutic Outcomes with Oral Semaglutide: A Patient-Centered Approach. Diabetes Spectr. 2021; 34: 7–19. https://doi.org/10.2337/ds20-0016.
46. Karedath J, Nall S, Kaur M, Lokhandwala A, Aqel YH, Maali Abusal A, et al. Comparative Effectiveness and Safety of Oral Versus Subcutaneous Semaglutide in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Cureus. 2025. https://doi.org/10.7759/cureus.82497.
47. Nain RA, Thomas DC. Lipohypertrophy prevalence and its associated risk factors in insulin-treated patients with type 2 diabetes in North Borneo, Malaysia. Belitung Nurs J. 2022; 8: 521–8. https://doi.org/10.33546/bnj.2246.
48. Abdel‐Moneim A, Ramadan H. Novel strategies to oral delivery of insulin: Current progress of nanocarriers for diabetes management. Drug Dev Res 2022; 83: 301–16. https://doi.org/10.1002/ddr.21903.
49. Mishra A, Waghamare S, Khanage SG. Acarbose-Loaded PLGA Microspheres: Efficient Encapsulation and Controlled Release. J Drug Deliv Ther. 2025; 15: 30–40. https://doi.org/10.22270/jddt.v15i6.7165.
50. Chavan T, Waghamare S, Kokare S, Madake A. Advanced Treatment of Type 1 Diabetes with Teplizumab: Mechanism and Clinical Efficacy. Asian J Med Princ Clin Pract. 2025; 8: 1–11. https://doi.org/10.9734/ajmpcp/2025/v8i1262.
51. Alqahtani MS, Kazi M, Alsenaidy MA, Ahmad MZ. Advances in Oral Drug Delivery. Front Pharmacol 2021;12:618411. https://doi.org/10.3389/fphar.2021.618411.
52. Myers J, Van Dam J, Imran M, Hashim M, Dhalla A. Preference for a Novel Oral Alternative to Parenterally Administered Medications. Patient Prefer Adherence. 2024; 18: 1547–62. https://doi.org/10.2147/PPA.S463354.
53. Adepu S, Ramakrishna S. Controlled Drug Delivery Systems: Current Status and Future Directions. Molecules 2021;26:5905. https://doi.org/10.3390/molecules26195905.
54. Meier JJ. Efficacy of Semaglutide in a Subcutaneous and an Oral Formulation. Front Endocrinol 2021; 12: 645617. https://doi.org/10.3389/fendo.2021.645617.
55. Boye K, Ross M, Mody R, Konig M, Gelhorn H. Patients’ preferences for ONCE‐DAILY oral versus ONCE‐WEEKLY injectable diabetes medications: The REVISE study. Diabetes Obes Metab. 2021; 23: 508–19. https://doi.org/10.1111/dom.14244.
56. Waghamare S, Jahed S, Kudhekar A, Patil P, Nikam P. Foundations of Artificial Intelligence in Pharmaceutical Preformulation. In: Waghamare S, Gaikwad A, Jahed S, Khanage S, editors. Artif. Intell. Preformulation Stud. Predict. Methods Mod. Pharm. Dev. Deep Science Publishing; 2026. https://doi.org/10.70593/978-93-7185-262-3_1.
57. Waghamare S, Gaikwad A, Jahed S, Khanage S, editors. Artificial Intelligence in Preformulation Studies: Predictive Methods For Modern Pharmaceutical Development. Deep Science Publishing; 2026. https://doi.org/10.70593/978-93-7185-262-3.
58. Gupta M, Srivastava N, Rai AK, Kathuria H. Recent advances in microneedles for drug delivery and theranostic application. Eur Polym J. 2025; 228: 113773. https://doi.org/10.1016/j.eurpolymj.2025.113773.
59. Kudhekar A, Waghamare S, Kadag P. Smart Separation Techniques: AI-Based Optimization in the Formulation Process. In: Waghamare S, Gaikwad A, Jahed S, Khanage S, editors. Artif. Intell. Preformulation Stud. Predict. Methods Mod. Pharm. Dev., Deep Science Publishing; 2026. https://doi.org/10.70593/978-93-7185-262-3_4.
60. Bernatoniene J, Stabrauskiene J, Kazlauskaite JA, Bernatonyte U, Kopustinskiene DM. The Future of Medicine: How 3D Printing Is Transforming Pharmaceuticals. Pharmaceutics 2025; 17: 390. https://doi.org/10.3390/pharmaceutics17030390.