A novel scalable fabrication process for the production of dissolving microneedle arrays
Tóm tắt
Microneedle arrays have emerged as an alternative method for transdermal drug delivery. Although micromolding using a centrifugation method is widely used to prepare microneedles in laboratory, few researchers were focused on manufacturing processes capable of facile scale-up. A novel female mold was initially designed in this study, namely double-penetration female mold (DPFM) with the pinpoints covered by waterproof breather membrane which was beneficial to reduce the influence of gas resistance and solution viscosity. In addition, DPFM-based positive-pressure microperfusion technique (PPPT) was proposed for the scale-up fabrication of dissolving microneedle arrays (DMNA). In this method, polymer solution and base solution were poured into the DPFM by pressure difference, followed by drying and demolding. The results of optimal microscopy and SEM revealed that the obtained microneedles were uniformly distributed conical-shaped needles. The skin penetration test showed that DMNA prepared using PPPT were able to penetrate the rat skin with a high penetration rate. To realize the transition of microneedles fabrication from laboratory to industry, an automatic equipment was further designed in this study. Different from micromolding method using centrifugation, the equipment based on PPPT and DPFM has superiorities in the scale-up fabrication of microneedles in a highly effective, controllable, and scalable way.
Tài liệu tham khảo
Garland MJ, Migalska K, Mahmood TM, Singh TR, Woolfson AD, Donnelly RF. Microneedle arrays as medical devices for enhanced transdermal drug delivery. Expert Rev Med Devices. 2011;8(4):459–82.
Lee K, Lee CY, Jung H. Dissolving microneedles for transdermal drug administration prepared by stepwise controlled drawing of maltose. Biomaterials. 2011;32(11):3134–40.
Coulman S, Allender C, Birchall J. Microneedles and other physical methods for overcoming the stratum corneum barrier for cutaneous gene therapy. Crit Rev Ther Drug Carrier Syst. 2006;23(3):205–58.
Vora LK, Donnelly RF, Larraneta E, Gonzalez-Vazquez P, Thakur RRS, Vavia PR. Novel bilayer dissolving microneedle arrays with concentrated PLGA nano-microparticles for targeted intradermal delivery: proof of concept. J Control Release. 2017;265:93–101.
Manikkath J, Manikkath A, Shavi GV, Bhat K, Mutalik S. Low frequency ultrasound and PAMAM dendrimer facilitated transdermal delivery of ketoprofen. J Drug Deliv Sci Technol. 2017;41:334–43.
Romgens AM, Rem-Bronneberg D, Kassies R, Hijlkema M, Bader DL, Oomens CWJ, et al. Penetration and delivery characteristics of repetitive microjet injection into the skin. J Control Release. 2016;234:98–103.
Elsabahy M, Foldvari M. Needle-free gene delivery through the skin: an overview of recent strategies. Curr Pharm Des. 2013;19(41):7301–15.
Ita K. Perspectives on transdermal electroporation. Pharmaceutics. 2016;8(1). https://doi.org/10.3390/pharmaceutics8010009.
Kaushik S, Hord AH, Denson DD, McAllister DV, Smitra S, Allen MG, et al. Lack of pain associated with microfabricated microneedles. Anesth Analg. 2001;92(2):502–4.
Cheung K, Das DB. Microneedles for drug delivery: trends and progress. Drug Deliv. 2016;23(7):2338–54.
Li JW, Zeng MT, Shan H, Tong CY. Microneedle patches as drug and vaccine delivery platform. Curr Med Chem. 2017;24(22):2413–22.
Lin S, Cai B, Quan G, Peng T, Yao G, Zhu C, et al. Novel strategy for immunomodulation: dissolving microneedle array encapsulating thymopentin fabricated by modified two-step molding technology. Eur J Pharm Biopharm. 2018;122:104–12.
Hirschberg HJ, van de Wijdeven GG, Kraan H, Amorij JP, Kersten GF. Bioneedles as alternative delivery system for hepatitis B vaccine. J Control Release. 2010;147(2):211–7.
Hong X, Wei L, Wu F, Wu Z, Chen L, Liu Z, et al. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine. Drug Des Devel Ther. 2013;7:945–52.
Zhang Q, Xu C, Lin S, Zhou H, Yao G, Liu H, et al. Synergistic immunoreaction of acupuncture-like dissolving microneedles containing thymopentin at acupoints in immune-suppressed rats. Acta Pharm Sin B. 2018;8:449–57. https://doi.org/10.1016/j.apsb.2017.12.006.
Yao G, Quan G, Lin S, Peng T, Wang Q, Ran H, et al. Novel dissolving microneedles for enhanced transdermal delivery of levonorgestrel: in vitro and in vivo characterization. Int J Pharm. 2017;534(1–2):378–86.
Wang QQ, Yao GT, Dong P, Gong ZH, Li G, Zhang KJ, et al. Investigation on fabrication process of dissolving microneedle arrays to improve effective needle drug distribution. Eur J Pharm Sci. 2015;66:148–56.
Yang S, Feng Y, Zhang L, Chen N, Yuan W, Jin T. A scalable fabrication process of polymer microneedles. Int J Nanomedicine. 2012;7:1415–22.
Park JH, Allen MG, Prausnitz MR. Polymer microneedles for controlled-release drug delivery. Pharm Res. 2006;23(5):1008–19.
Nakata Y, Xu X, Roth S, Neuenschwander B, Sato Y, Tsukamoto M, et al. Analysis of laser ablation dynamics of CFRP in order to reduce heat affected zone. Proc SPIE. 2014;8967:89670M.
Ito Y, Hagiwara E, Saeki A, Sugioka N, Takada K. Feasibility of microneedles for percutaneous absorption of insulin. Eur J Pharm Sci. 2006;29(1):82–8.
Caffarel-Salvador E, Kearney MC, Mairs R, Gallo L, Stewart SA, Brady AJ, et al. Methylene blue-loaded dissolving microneedles: potential use in photodynamic antimicrobial chemotherapy of infected wounds. Pharmaceutics. 2015;7(4):397–412.
Larraneta E, Moore J, Vicente-Perez EM, Gonzalez-Vazquez P, Lutton R, Woolfson AD, et al. A proposed model membrane and test method for microneedle insertion studies. Int J Pharm. 2014;472(1–2):65–73.
Park J, Allen M, Prausnitz M. Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J Control Release. 2005;104(1):51–66.