Sustained transdermal delivery of NO donor using PLGA PVP/PVA core-shell microneedles for primary osteoporosis treatment

• Main Authors: Chia-ChenChang, 張家振
• Other Authors: Mei-Chin Chen
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/eznb4s

碩士 === 國立成功大學 === 化學工程學系 === 107 === In postmenopausal women, estrogen deficiency causes osteoclasts over activation, which easily suffers from primary osteoporosis. Low concentration of nitric oxide can regulate the immune system, which causes thymocytes apoptosis, reduces T cell proliferation, and slows down tumor necrosis factor-alpha (TNF-α) to stimulate osteoclasts differentiation, thus suppressing bone resorption. In this study, we developed a core-shell microneedle (MN) system for sustained transdermal delivery of molsidomine, a NO donor and evaluated its feasibility for treatment of osteoporosis. In the MN system, [poly(lactic-co-glycolic acid), PLGA] was used as a core material to encapsulate molsidomine; [poly(vinyl alcohol) and poly(vinyl pyrrolidone) blends, PVP/PVA] was selected as a shell material to provide mechanical strength for improving MN insertion capability. The in vitro drug release study showed that MN made by PLGA with LA:GA = 85:15 provided an approximate zero-order release profile (R2 = 0.97, n = 5) for two weeks and no initial burst release or second release occurred. Compared to the MN without the shell, the PVP/PVA shell can improve the insertion depth from 665 ± 142 μm to 948 ± 35 μm (n = 6), demonstrating the shell enhance the MN puncture stability. Ovariectomized (OVX) Sprague Dawley rat was used as a model of postmenopausal osteoporosis to evaluate the MN efficacy. The animals were divided into four groups: untreated (OVX), low-dose (two patches per two weeks) MN, high-dose MN (three patches per two weeks), and estradiol (E2, daily injection) treated groups. After 8 weeks of treatment, the bone mineral density and other bone parameters of the high-dose MN group were significantly higher than those of the untreated group, and there was no statistical difference compared to the E2 group. Additionally, the TNF-α levels were significantly reduced in both MN groups. These results demonstrated that using the PLGA-PVP/PVA core-shell microneedle for sustained release of molsidomine could be a potential therapeutic strategy for the treatment and prevention of postmenopausal bone loss.