A. Lakshmi Usha, M. Kusuma Kumari, E. Radha Rani, A.V.S. Ksheera Bhavani
A. Lakshmi Usha1*, M. Kusuma Kumari1, E. Radha Rani1, A.V.S. Ksheera Bhavani2
1Department of Pharmaceutics, Maharajah’s Collage of Pharmacy, Vizianagaram, A. P., India.
2Department of Pharmaceutics, Sri Venkateswara College of Pharmacy, Madhapur, Hyderabad, Telanaga.
Volume - 10,
Issue - 4,
Year - 2020
The barrier properties of the topmost layer of the skin, stratum corneum have significant limitations for successful systemic delivery of a wide range of therapeutic molecules, especially macromolecules and genetic material. One solution is to utilize microneedles (MNs), which are capable of painlessly traversing through the stratum corneum and directly translocating protein drugs into the systemic circulation. This strategy involves the use of micron sized needles fabricated from different materials and using different geometries to create transient aqueous conduits across the skin. Microneedles in isolation, or in combination with other enhancing strategies, have been shown to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo. MNs can be designed to incorporate appropriate structural materials as well as therapeutics or formulations with tailored physicochemical properties. This platform technique has been applied to deliver drugs both locally and systemically in applications ranging from vaccination to diabetes and cancer therapy. As an alternative to hypodermic needles, coated polymer microneedles (MNs) are able to deliver drugs to subcutaneous tissues after being inserted into the skin. The dip-coating process is a versatile, rapid fabricating method that can form coated MNs in a short time. However, it is still a challenge to fabricate coated MNs with homogeneous and precise drug doses in the dip-coating process. This review article focuses on recent and potential future developments in microneedle technologies. This will include the detailing of progress made in microneedle design, an exploration of the challenges faced in this field and potential forward strategies to embrace the exploitation of microneedle methodologies, while considering the inherent safety aspects of such therapeutic tools. The clinical potential and future translation of MNs are also discussed.
Cite this article:
A. Lakshmi Usha, M. Kusuma Kumari, E. Radha Rani, A.V.S. Ksheera Bhavani. A Novel Technique for Intra Transdermal Delivery of Drugs – Coated Polymeric Needles. Asian J. Pharm. Tech. 2020; 10(4):289-295. doi: 10.5958/2231-5713.2020.00048.3
1. Aoyagi S, Izumi H, Fukuda M. Biodegradable polymer needle with various tip angles and consideration on insertion mechanism of mosquito’s proboscis. Sensors and Actuators A: Physical. 2008; 143(1):20–28.
2. Aoyagi S, Izumi H, Isono Y, et al. Laser fabrication of high aspect ratio thin holes on biodegradable polymer and its application to a microneedle. Sensors and Actuators A: Physical. 2007;139(1-2):293–302.
3. Bal SM, Ding Z, Kersten GF, et al. Microneedle-based transcutaneous immunisation in mice with N-trimethyl chitosan adjuvanted diphteria toxoid formulations. Pharmaceutical Research. 2010; 27(9):1837–1847.
4. Bal SM, Caussin J, Pavel S, et al. In vivo assessment of safety of microneedle arrays in human skin. European Journal of Pharmaceutical Sciences. 2008; 35(3):193–202.
5. Banga AK. Therapeutic Peptides and Proteins: Formulation, Processing and Delivery Systems. CRC Press Taylor and Francis Group; Boca Raton: 2006.
6. Banga AK. Microporation applications for enhancing drug delivery. Expert Opinion on Drug Delivery. 2009;6(4):343–354.
7. Birchall JC, Clemo R, Anstey A, et al. Microneedles in clinical practice - an exploratory study into the opinions of healthcare professionals and the public. Pharmaceutical Research. 2011; 28(1):95–106.
8. Bodhale WD, Nisar A, Afzulpurkar N. Structural and microfluidic analysis of hollow side-open polymeric microneedles for transdermal drug delivery applications. Microfluid Nanofluid. 2010;8: 373–392.
9. Boehm RD, Miller PR, Singh R, et al. Indirect rapid prototyping of antibacterial acid anhydride copolymer microneedles. Biofabrication. 2012; 4(1):011002.
10. Brunner M, Derendorf H. Clinical microdialysis: Current applications and potential use in drug development. Trends in Analytical Chemistry. 2006; 25(7):674–680.
11. Bystrova S, Luttge R. Micromolding for ceramic microneedle arrays. Microelectronic Engineering. 2011; 88(8):1681–1684.
12. Chabri F, Bouris K, Jones T, et al. Microfabricated silicon microneedles for nonviral cutaneous gene delivery. British Journal of Dermatology. 2004; 150(5):869–877.
13. Chandrasekaran S, Brazzle JD, Frazier AB. Surface micromachined metallic microneedles. Journal of Microelectromechanical Systems. 2003; 12(3):281–288. [Google Scholar]
14. Chen H, Zhu H, Zheng J, et al. Iontophoresis-driven penetration of nanovesicles through microneedle-induced skin microchannels for enhancing transdermal delivery of insulin. Journal of Controlled Release. 2009a; 139(1):63–72.
15. Lhernould, M.S.; Deleers, M.; Delchambre, A. Hollow polymer microneedles array resistance and insertion tests. Int. J. Pharm. 2015, 480, 152–157.
16. Kim, K.S.; Ita, K.; Simon, L. Modelling of dissolving microneedles for transdermal drug delivery: theoretical and experimental aspects. Eur. J. Pharm. Sci. 2015, 68, 137–143.
17. Danso, M.O.; Berkers, T.; Mieremet, A.; Hausil, F.; Bouwstra, J.A. An ex vivo human skin model for studying skin barrier repair. Exp. Dermatol. 2015, 24, 48–54.
18. Danso, M.O.; van Drongelen, V.; Mulder, A.; Gooris, G.; van Smeden, J.; El Ghalbzouri, A.; Bouwstra, J.A. Exploring the potentials of nurture: 2nd and 3rd generation explant human skin equivalents. J. Dermatol. Sci. 2015, 77, 102–109.
19. 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.
20. 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.
21. Flaten, G.E.; Palac, Z.; Engesland, A.; Filipović-Grčić, J.; Vanić, Ž.; Škalko-Basnet, N. In vitro skin models as a tool in optimization of drug formulation. Eur. J. Pharm. Sci. 2015, 75, 10–24.
22. Olatunji, O.; Das, D.B.; Garland, M.J.; 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.
23. 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.
24. Kaur, M.; Ita, K.B.; Popova, I.E.; Parikh, S.J.; Bair, D.A. Microneedle-assisted delivery of verapamil hydrochloride and amlodipine besylate. Eur. J. Pharm. Biopharm. 2014, 86, 284–291.
25. Coulman S, Allender C, Birchall J. Microneedles and other physical methods for overcoming the stratum corneum barrier for cutaneous gene therapy. Critical Reviews in Therapeutic Drug Carrier Systems. 2006a; 23(3):205–258.
26. Coulman SA, Barrow D, Anstey A, et al. Minimally invasive cutaneous delivery of macromolecules and plasmid DNA via microneedles. Current Drug Delivery. 2006b; 3(1):65–75.
27. Coulman SA, Birchall JC, Alex A, et al. In vivo, in situ imaging of microneedle insertion into the skin of human volunteers using optical coherence tomography. Pharmaceutical Research. 2011;28(1):66–81.
28. Crichton ML, Ansaldo A, Chen X, et al. The effect of strain rate on the precision of penetration of short densely packed microprojection array patches coated with vaccine. Biomaterials. 2010; 31(16):4562–4572.
29. Davis SP, Martanto W, Allen MG, et al. Hollow metal microneedles for insulin delivery to diabetic rats. IEEE Trans. Biomed. Eng. 2005; 52(5):909–915.
30. Davis SP, Landis BJ, Adams ZH, et al. Insertion of microneedles into skin: measurement and prediction of insertion force and needle fracture force. Journal of Biomechanics. 2004; 37(8):1155–1163.
31. Ding Z, Verbaan FJ, Bivas-Benita M, et al. Microneedle arrays for the transcutaneous immunization of diphtheria and influenza in BALB/c mice. Journal of Controlled Release. 2009; 136(1):71–78.
32. Donnelly RF, Garland MJ, Morrow DI, et al. Optical coherence tomography is a valuable tool in the study of the effects of microneedle geometry on skin penetration characteristics and in-skin dissolution. Journal of Controlled Release. 2010; 147(3):333–341.
33. Donnelly RF, Majithiya R, Singh TR, et al. Design, Optimization and Characterisation of Polymeric Microneedle Arrays Prepared by a Novel Laser-Based Micromoulding Technique. Pharmaceutical Research. 2011; 28(1):41–57.
34. Donnelly RF, Morrow DI, McCarron PA, et al. Microneedle-mediated intradermal delivery of 5-aminolevulinic acid: potential for enhanced topical photodynamic therapy. Journal of Controlled Release. 2008; 129(3):154–162.