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

Abstract

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-?) 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-? 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

Date of Award	2019
Original language	English
Supervisor	Mei-Chin Chen (Supervisor)