Chitosan–β-glycerophosphate thermogelling microneedles for transdermal contraceptive delivery of levonorgestrel

This study presents the development of dissolving levonorgestrel-loaded 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 controlled drug release. LMNs fabricated using poly dimethyl siloxane moulds exhibited uniform, sharp structures as confirmed by scanning electron microscopy. Fourier transform infra-red and X-ray diffraction analyses demonstrated chemical compatibility and physical stability of LNG within the matrix. The optimised LMNs showed significant mechanical strength (<i>p</i> < 0.05) and high insertion efficiency (<i>F</i> = 17.83, <i>p</i> = 3.03 × 10^-8) across Parafilm^® layers and fully dissolved within 30 min in porcine skin. <i>Ex vivo</i> studies revealed sustained LNG release (70.86% ± 0.42%) over 48 h, outperforming a topical gel (42.33% ± 0.91%). Drug release followed first-order kinetics (<i>R</i>² = 0.996) and non-Fickian diffusion (<i>n</i> = 0.79), indicating a combined diffusion-erosion mechanism. <i>In vivo</i> evaluation in Wistar rats showed significant contraceptive efficacy, with reduced implantation sites (0.5 ± 0.55) and uterine thickness (3.66 ± 0.51 mm; <i>p</i> < 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.