Popat S. Kumbhar, Tejaswini P. Jadhav, Swapnil S. Chopade, Tejas T. Gavade, Rushikesh C. Sorate, Tejaswini U. Shinde, Pratik P. Maske, John I. Disouza, Arehalli S. Manjappa
Popat S. Kumbhar*, Tejaswini P. Jadhav, Swapnil S. Chopade, Tejas T. Gavade, Rushikesh C. Sorate, Tejaswini U. Shinde, Pratik P. Maske, John I. Disouza, Arehalli S. Manjappa
Tatyasaheb Kore College of Pharmacy, Warananagar, Tal: Panhala, Dist: Kolhapur, Maharashtra, India, 416113.
Volume - 11,
Issue - 1,
Year - 2021
Nowadays, biotherapeutics are playing an essential job in the treatment of an assortment of diseases such as cancer, infectious diseases and etc. Be that as it may, the inherent properties of therapeutic proteins stay a noteworthy obstruction for transdermal delivery, including their moderately huge molecule size and susceptibility to degradation. These issues of biotherapeutics can be overwhelmed by utilizing microneedles (MNs), which are prepared to do easily navigating the horny layer and legitimately moving protein drugs into the systematic circulation. MNs are intended to incorporate appropriate structural materials yet as therapeutics or formulations with tailored physicochemical properties. This platform has been applied to convey drugs both locally and systemically in applications beginning from vaccination to diabetes and cancer therapy. The present review focuses on importance of MN technology in transdermal delivery of biologics, mechanism of transdermal delivery of drugs through MNs, different materials used for the fabrication of MNs, potential challenges associated with transdermal delivery of different biologics through MNs. Moreover, improved performance of biologics delivered through the MNs and biologics MNs in clinical trials is also summarized. Thus, MNs as promising tool which displayed profound guarantee for biomedical applications.
Cite this article:
Popat S. Kumbhar, Tejaswini P. Jadhav, Swapnil S. Chopade, Tejas T. Gavade, Rushikesh C. Sorate, Tejaswini U. Shinde, Pratik P. Maske, John I. Disouza, Arehalli S. Manjappa. Microneedles: An Advanced approach for Transdermal Delivery of Biologics. Asian J. Pharm. Res. 2021; 11(1):46-54. doi: 10.5958/2231-5691.2021.00010.1
Popat S. Kumbhar, Tejaswini P. Jadhav, Swapnil S. Chopade, Tejas T. Gavade, Rushikesh C. Sorate, Tejaswini U. Shinde, Pratik P. Maske, John I. Disouza, Arehalli S. Manjappa. Microneedles: An Advanced approach for Transdermal Delivery of Biologics. Asian J. Pharm. Res. 2021; 11(1):46-54. doi: 10.5958/2231-5691.2021.00010.1 Available on: https://asianjpr.com/AbstractView.aspx?PID=2021-11-1-10
1. Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 2015; 33: 941-51. doi: 10.1038/nbt.3330
2. Jatav VS, Saggu JS, Sharma AK, et al. Design, Formulation and in vitro Drug Release from Transdermal Patches containing Nebivolol Hydrochloride as Model Drug. Asian J. Pharm. Res. 2012; 2(4): 136-141.
3. Respaud R, Vecellio L, Diot P. Nebulization as a delivery method for mAbs in respiratory diseases. Expert Opin. Expert Opin. Drug Delivery. 2015; 12:1027-1039.
4. Praveena CH, Pramod K, Ajithkumar KC. Dendritic cell vaccine for cancer therapy. Res. J. Pharmacology and Pharmacodynamics.2016; 8(3): 141-147.
5. Waghule T, Singhvi G, Gupta G. Microneedles: A smart approach and increasing potential for transdermal drug delivery system. Biomedicine and Pharmacotherapy. 2019; 109: 1249-1258.
6. Kim Y, Park J, Prausnitz M. Microneedles for drug and vaccine delivery. Adv. Drug Deliv. Rev. (2012); 64: 1547–1568.
7. Donnelly RF, McCrudden MTC, Zaid AA, Larrañeta E, McAlister E, Courtenay AJ, Kearney MC, Singh TRR, McCarthy HO, et al. Hydrogel-forming microneedles prepared from ‘super swelling’ polymers combined with lyophilised wafers for transdermal drug delivery. PLoS One. 2014; 9: e111547.
8. Ma Y, Tao W, Krebs SJ, Sutton WF, Haigwood NL, Gill HS. Vaccine Delivery to the oral cavity using coated microneedles induces systemic and mucosal immunity. Pharm. Res. 2014; 31:1-11.
9. Hoang MT, Ita KB, Bair DA. Solid Microneedles for transdermal delivery of amantadine hydrochloride and pramipexole dihydrochloride. Pharmaceutics. 2015; 7(4):379-396.
10. Mansoor I, Liu Y, Häfeli U, Stoeber B. Arrays of hollow out-of-plane microneedles made by metal electrodeposition onto solvent cast conductive polymer structures. J. Micromech and Microeng. 2013; 23 (8): 1-10.
11. Jiang J, Gill HS, Ghate D, McCarey BE, Patel SR, Edelhauser HF, Prausnitz MR. Coated microneedles for drug delivery to the eye. Investigative ophthalmology and visual science. 2007; 48 (9): 4038-4043.
12. Gupta J, Park SS, Bondy B, Felner EI, Prausnitz MR. Infusion pressure and pain during microneedle injection into skin of human subjects. Biomaterials. 2011; 32 (28): 6823-6831.
13. Jiang J, Gill HS, Ghate D, McCarey BE, Patel SR, Edelhauser HF, et al. Coated microneedles for drug delivery to the eye. Investigative ophthalmology and visual science. 2007; 48(9):4038-4043.
14. Zhu DD, Wang QL, Liu XB, GuoXD. Rapidly Separating Microneedles for Transdermal Drug Delivery. Acta biomaterialia. 2016; 41(1):1-8.
15. Van Damme P, Osterhuis-Kafeja F, Van der Wielen M, Almagor Y, Sharon O, Levin Y. Safety and efficacy of a novel microneedle device for dose sparing intradermal influenza vaccination in healthy adults. Vaccine. 2009; 27 (3):454-459.
16. Wilke N, Mulcahy A, Ye SR, Morrissey A. Process optimization and characterization of silicon microneedles fabricated by wet etch technology. Microelectronics Journal 2005; 36 (7):650-656.
17. Nagadev C, Rao M, Venkatesh P, Hepcykalarani D, Prema R. A Review on transdermal drug delivery systems. Asian J. Res. Pharm. Sci. 2020; 10(2):109-114.
18. Banga AK. Microporation applications for enhancing drug delivery. Expert Opinion on Drug Delivery. 2009; 6 (4):343-354.
19. Gupta J, Gill HS, Andrews SN, Prausnitz MR. Kinetics of skin resealing after insertion of microneedles in human subjects. Journal of Controlled Release. 2011; 154 (2):148-155.
20. McCarthy PT, Otto KJ, Rao MP. Robust penetrating microelectrodes for neural interfaces realized by titanium micromachining. Biomedical Microdevices. 2011; 13(3):503-515.
21. Rajashri RK, Dipti GP. The microneedle patches: An innovative approach. Asian J. Pharm. Tech. 2015; 5(4): 195-200.
22. Invernale MA, Tang BC, York RL, Le L, Hou DY, Anderson DG. Microneedle electrodes toward an amperometric glucose sensing smart patch. Advanced healthcare materials 2014; 3 (3):338-342.
23. Bhattacharya S, Kam DH, Song L, Mazumder J. Characterization of individual microneedles formed on alloy surfaces by femtosecond laser ablation. Metallurgical and Materials Transactions. 2012; 43(8):2574-2580.
24. Amalraju D, Dawood AS. Mechanical strength evaluation analysis of stainless steel and titanium locking plate for femur bone fracture. IRACST-Engineering Science and Technology: An International Journal (ESTIJ). 2012; 2(3):381-388.
25. Martanto W, Moore JS, Kamath R, Wang PM, O'Neal JM. Prausnitz MR, et al. Microinfusion using hollow microneedles. Pharmaceutical research. 2006; 23(1):104-113.
26. Wang PM, Cornwell M, Hill J, Prausnitz MR. Precise microinjection into skin using hollow microneedles. Journal of Investigative Dermatology. 2006; 126 (5):1080-1087.
27. Theiss F, Apelt D, Brand B, Kutter A, Zlinszky K, Bohner M, et al. Biocompatibility and resorption of a brushite calcium phosphate cement. Biomaterials. 2005; 26 (21):4383-4394.
28. Bystrova S, Luttge R. Micromolding for ceramic microneedle arrays. Microelectronic Engineering. 2011; 88(8):1681-1684.
29. Luangveera W, Jiruedee S, Mama W, Chiaranairungroj M, Pimpin A, Palaga T, et al. Fabrication and characterization of novel microneedles made of a polystyrene solution. Journal of the Mechanical Behavior of Biomedical Materials. 2015; 50: 77-81.
30. Grayson AC, Voskerician G, Lynn A, Anderson JM, Cima MJ, Langer R. Differential degradation rates in vivo and in vitro of biocompatible poly (lactic acid) and poly (glycolic acid) homo-and co-polymers for a polymeric drug delivery microchip. Journal of Biomaterials Science Polymer Edition. 2004; 15(10):1281-1304.
31. McGrath MG, Vucen S, Vrdoljak A, Kelly A, O’Mahony C, Crean AM, et al. Production of dissolvable microneedles using an atomised spray process: effect of microneedle composition on skin penetration. European Journal of Pharmaceutics and Biopharmaceutics. 2014; 86 (2):200-211.
32. Gill Harvinder S, Prausnitz Mark R. Pocketed microneedles for drug delivery to the skin. J Phys Chem Solids. 2008; 69(5-6):1537-1541.
33. Bhatnagar S, Chawla SR, Kulkarni OP, Venuganti VV. Zeinmicroneedles for transcutaneous vaccine delivery: fabrication, characterization, and in vivo evaluation using ovalbumin as the model antigen . ACS Omega. 2017; 4(2):1321-1332.
34. Ismail HR, Narayanaswamy VB, Injamamul H, Mohibul H. Design and Evaluation of Transdermal Patches Containing Risperidone. Asian J. Res. Pharm. Sci. 2016; 6(4): 208-222.
35. Watanabe T, Hagino K and Sato T. Evaluation of the effect of polymeric microneedle arrays of varying geometries in combination with a high-velocity applicator on skin permeability and irritation. Biomedical Microdevices. 2014;16(5):91-110.
36. Lippmann JM, Geiger EJ and Pisano AP. Polymer investment molding: Method for fabricating hollow, microscale parts Sens. Actuators Phys. 2007; 134: 2-10.
37. Li J, Zhou Y, Yang J, Ye R, Gao J, Ren L et al. Fabrication of gradient porous microneedle array by modified hot embossing for transdermal drug delivery. Materials Science and Engineering C. 2019; 96:576-582.
38. Norman JJ, Choi SO, Tong NT, Aiyar AR, Patel SR, Prausnitz MR, et al. Hollow microneedles for intradermal injection fabricated by sacrificial micromoldingand selective electrodeposition. Biomedical Microdevices. 2013; 15(2):203-210.
39. Park SC, Kim MJ, Baek SK, Park JH, Choi SO. Spray-formed layered polymer microneedles for controlled biphasic drug delivery. Polymers. 2019; 11(2): 1-13.
40. Sullivan SP, Murthy N and Prausnitz MR. Minimally invasive protein delivery with rapidly dissolving polymer microneedles. Advanced Materials. 2008; 20(5): 933-938.
41. Pankaj RD, Chauriya CB, Umredkar RC. Painless insulin drug delivery systems -A Review. Asian J. Res. Pharm. Sci. 2017; 7(1):01-07.
42. Beedha. S, Satyanarayana TK, Mounika GS, Sravika K, Krishna MM. Formulation and Characterization of Tramadol HCl Transdermal Patch. Asian J. Pharm. Tech. 2018; 8(1):23-28.
43. Kochhar JS, Anbalagan P, Shelar SB, Neo JK, Iliescu C, Kang L. Direct microneedle array fabrication off a photomask to deliver collagen through skin. Pharm. Res. 2014; 31:1724.
44. Johnson AR, Caudill CL, Tumbleston JR, Bloomquist CJ, Moga KA, Mecham SJ, et al. Single-step fabrication of computationally designed microneedles by continuous liquid interface production. PLoS ONE. 2016; 11(9):2-17.
45. Gittard SD, Ovsianikov A, Chichkov BN, Doraiswamy A and Narayan RJ. Two-photon polymerization of microneedles for transdermal drug delivery. Expert Opin. Drug Delivery. 2010; 7(4): 513-33.
46. Gill HS, Prausnitz MR. Coated microneedles for transdermal delivery. J. Control Release. 2007; 117(2): 227-37.
47. Sandip SK, Siraj NS, Narendra BP, Ketan BP. Novel Molecule of Protein Tyrosine Kinase Enzyme Inhibitor in Treatment of Breast Cancer: Neratinib Maleate. Asian J. Res. Pharm. Sci. 2020; 10(2):100-102.
48. Babu VR, Syeda RN, Nivethithai P, Areefulla SH. Approaches and Challenges of Protein and Peptide Drug Delivery Systems. Research J. Pharm. and Tech. 2010; 3(2):379-384.
49. Ratanji KD, Derrick JP, Dearman RJ, Kimber I. Immunogenicity of therapeutic proteins: Influence of aggregation. J Immunotoxicol. 2014; 11(2):99-109.
50. Rothe A, Power BE, Hudson PJ. Therapeutic advances in rheumatology with the use of recombinant proteins. Nat Clin Pract Rheumatol. 2008; 4(11):605-14.
51. Ito Y, Kashiwara S, Fukushima K, Takada K. Two-layered dissolving microneedles for percutaneous delivery of sumatriptan in rats. Drug Dev Ind Pharm. 2011; 37(12):1387-93.
52. Cobo I, Li M, Sumerlin BS, Perrier S. Smart hybrid materials by conjugation of responsive polymers to biomacromolecules. Nature medicine. 2015; 14(2):143-59.
53. Chen W, Tian R, Xu C, Yung BC, Wang G, Liu Y, et al. Microneedle-array patches loaded with dual mineralized protein/peptide particles for type 2 diabetes therapy. Nature communications. 2017; 8:1777.
54. Yang PY, Zou H, Chao E, Sherwood L, Nunez V, Keeney M, et al. Engineering a long-acting, potent GLP- 1 analog for microstructure-based transdermal delivery. Proceedings of the National Academy of Sciences of the United States of America. 2016; 113(15):4140-5.
55. Donnelly RF, Morrow DIJ, Singh TRR, Migalska K, McCarron PA, O'Mahony C, et al. Processing difficulties and instability of carbohydrate microneedle arrays. Drug Dev Ind Pharm. 2009; 35:1242-54.
56. Martanto W, Davis SP, Holiday NR, Wang J, Gill HS, Prausnitz MR, et al. Transdermal delivery of insulin using microneedles in vivo. Pharm Res. 2004; 21(6):947 52.
57. Couzin-Frankel J. Cancer immunotherapy. Science. 2013; 342:1432-3.
58. Aaron JC, Maelíosa TC, Kathryn JM, Helen O. McCarthy, Ryan F. Donnelly. Microneedle-mediated transdermal delivery of bevacizumab. Mol. Pharmaceutics 2018; 15(8): 3545-3556.
59. Giudice EL, Campbell JD. Needle-free vaccine delivery. Adv Drug Deliv Rev. 2006; 58(1):68 89.
60. Weldon WC, Martin MP, Zarnitsyn V, Wang B, Koutsonanos D, Skountzou I, et al. Microneedle vaccination with stabilized recombinant influenza virus hemagglutinin induces improved protective immunity. Clinical and vaccine immunology: CVI. 2011; 18:647-54.
61. Aoife MR, Maelíosa TC, Alice VD, Rebecca JI, Adrien K, Ryan F. Donnelly, et al. Design and characterisation of a dissolving microneedle patch for intradermal vaccination with heat-inactivated bacteria: A proof of concept study. International Journal of Pharmaceutics. 2018; 549(1-2):87-95.
62. Ali AA, McCrudden CM, McCaffrey J, McBride JW, Cole G, Dunne NJ, Robson T, Kissenpfennig A, Donnelly RF, McCarthy HO. DNA vaccination for cervical cancer; A novel technology platform of RALA mediated gene delivery via polymeric microneedles. Nanomedicine. 2017; 13(3):921-932. doi: 10.1016/j.nano.2016.11.019
63. Widera G, Johnson J, Kim L, Libiran L, Nyam K, Daddona PE, et al. Effect of delivery parameters on immunization to ovalbumin following intracutaneous administration by a coated microneedle array patch system. Vaccine. 2006; 24(10):1653-64.
64. Cormier M, Johnson B, Ameri M, Nyam K, Libiran L, Zhang DD, et al. Transdermal delivery of desmopressin using a coated microneedle array patch system. J Control Release. 2004; 97(3):503-11.
65. Ameri M, Wang X, Maa YF. Effect of irradiation on parathyroid hormone PTH (1-34) coated on a novel transdermal microprojection delivery system to produce a sterile product adhesive compatibility. J Pharm Sci. 2009; 99(4):2123-34.
66. Chen X, Prow TW, Crichton ML, Jenkins DW, Roberts MS, Frazer IH, et al. Dry-coated microprojection array patches for targeted delivery of immunotherapeutics to the skin. J Control Release. 2009; 139(3):212-20.
67. Matriano JA, Cormier M, Johnson J, Young WA, Buttery M, Nyam K, et al. Macroflux microprojection array patch technology: A new and efficient approach for intracutaneous immunization. Pharm Res.2002; 19(1):63-70.
68. Marin A, Andrianov AK. Carboxymethylcellulose-Chitosan-coated microneedles with modulated hydration properties. J Appl Polym Sci. 2011; 121:395-401.
69. Andrianov AK, Marin A, DeCollibus DP. Microneedles with intrinsic immunoadjuvant properties: Microfabrication, protein stability, and modulated release. Pharm Res. 2011; 28(1):58-65.
70. Andrianov AK, DeCollibus DP, Gillis HA, Kha HH, Marin A, Prausnitz MR, et al. Poly[di(carboxylatophenoxy)phosphazene] is a potent adjuvant for intradermal immunization. Proc Natl Acad Sci USA. 2009; 106(45):18936-41.
71. Lee JW, Choi SO, Felner EI, Prausnitz MR. Dissolving microneedle patch for transdermal delivery of human growth hormone. Small. 2011; 7(4):531-9.
72. Lee JW, Park J-H, Prausnitz MR. Dissolving microneedles for transdermal drug delivery. Biomaterials. 2008; 29(13):2113-24.
73. Fukushima K, Yamazaki T, Hasegawa R, Ito Y, Sugioka N, Takada K. Pharmacokinetic and pharmacodynamic evaluation of insulin dissolving microneedles in dogs. Diabetes Technol Ther. 2010; 12(6):465-74.
74. Ito Y, Hagiwara E, Saeki A, Sugioka N, Takada K. Sustained-release self-dissolving micropiles for percutaneous absorption of insulin in mice. J Drug Target. 2007; 15(3):323-6.
75. Ito Y, Yoshimitsu J, Shiroyama K, Sugioka N, Takada K. Self-dissolving microneedles for the percutaneous absorption of EPO in mice. J Drug Target. 2006; 14(15):255-61.
76. Donnelly RF, Morrow DIJ, Singh TRR, Migalska K, McCarron PA, O'Mahony C, et al. Processing difficulties and instability of carbohydrate microneedle arrays. Drug Dev Ind Pharm. 2009; 35(10):1242-54.
77. Matsuo K, Hirobe S, Yokota Y, Ayabe Y, Seto M, Quan YS, et al. Transcutaneous immunization using a dissolving microneedle array protects against tetanus, diphtheria, malaria, and influenza. J Control Release 2012;160(3):495-501.
78. Chu LY, Prausnitz MR. Separable arrowhead microneedles. J Control Release. 2011; 149(3):242 9.
79. Li G, Badkar A, Nema S, Kolli CS, Banga AK. In vitro transdermal delivery of therapeutic antibodies using maltose microneedles. Int J Pharm. 2009; 368(1-2):109-15.
80. Park J-H, Allen MG, Prausnitz MR. Polymer Microneedles for controlled-release drug delivery. PharmRes. 2006; 23(5):1008-19.
81. Migalska K, Morrow DIJ, Garland MJ, Thakur R, Woolfson AD, Donnelly RF. Laser-engineered dissolving microneedle arrays for transdermal macromolecular drug delivery. Pharm Res. 2011; 28(8):1919-30.
82. Ling M-H, Chen M-C. Dissolving polymer microneedle patches for rapid and efficient transdermal delivery of insulin to diabetic rats. Acta Biomater. 2013; 9(11):8952-61.
83. De Muth PC, Min Y, Irvine DJ, Hammond PT. Implantable silk composite microneedles for programmable vaccine release kinetics and enhanced immunogenicity in transcutaneous immunization. Adv Health Mater. 2014;3(1):47-58.
84. Yu J, Zhang Y, Ye Y, DiSanto R, Sun W, Ranson D, et al. Microneedle-array patches loaded with hypoxia sensitive vesicles provide fast glucose-responsive insulin delivery. Proceedings of the National Academy of Sciences. 2015; 112(27):8260-5.
85. Ye Y, Wang J, Hu Q, Hochu GM, Xin H, Wang C, et al. Synergistic transcutaneous immunotherapy enhances antitumor immune responses through delivery of checkpoint inhibitors. ACS Nano. 2016; 10(9):8956-63.