Chitosan-β-Glycerophosphate Thermo-gelling Microneedles for Transdermal Contraceptive Delivery of Levonorgestrel

This study presents the development of dissolving microneedles (LMNs) incorporating a chitosan-β-glycerophosphate thermogelling system for sustained transdermal delivery of levonorgestrel (LNG) as a contraceptive. Polyvinylpyrrolidone K90 and Dextran 40 were included to enhance mechanical strength and control drug release. LMNs fabricated using PDMS molds exhibited uniform, sharp structures as confirmed by SEM. FTIR and XRD analyses demonstrated chemical compatibility and physical stability of LNG within the matrix. The optimized LMNs showed significant mechanical strength (P < 0.05) and high insertion efficiency (F = 17.83, P = 3.03 × 10−8) across Parafilm® layers and fully dissolved within 30 minutes in porcine skin. Ex vivo studies revealed sustained LNG release (70.86 ± 0.42%) over 48 hours, outperforming a topical gel (42.33 ± 0.91%). Drug release followed first-order kinetics (R2 = 0.996) and non-Fickian diffusion (n = 0.79), indicating a combined diffusion-erosion mechanism. In vivo evaluation in Wistar rats showed significant contraceptive efficacy, with reduced implantation sites (0.5 ± 0.55) and uterine thickness (3.66 ± 0.51 mm; p < 0.0001), comparable to oral LNG. These results highlight LMNs as a promising, minimally invasive platform for long-acting transdermal contraception, offering improved bioavailability, patient compliance, and therapeutic effectiveness.