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

IF 3.9 4区 医学 Q1 PHARMACOLOGY & PHARMACY
Chethan Kumar K B, Sateesha S B, Ankith N A, Rajamma A J, Durgashree Diwakar, Girija E K, Likhitha C N
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Abstract

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 (p < 0.05) and high insertion efficiency (F = 17.83, p = 3.03 × 10-8) across Parafilm® layers and fully dissolved within 30 min in porcine skin. Ex vivo 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 (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.

壳聚糖-β-甘油磷酸酯热凝胶微针经皮给药左炔诺孕酮。
本研究提出了一种溶解微针(lmn)的发展,该微针包含壳聚糖-β-甘油磷酸酯热凝胶系统,用于持续经皮给药左炔诺孕酮(LNG)作为一种避孕药。加入聚乙烯吡咯烷酮K90和葡聚糖40以增强机械强度和控制药物释放。SEM证实,使用PDMS模具制造的LMNs具有均匀,锋利的结构。FTIR和XRD分析证明了LNG在基体中的化学相容性和物理稳定性。优化后的LMNs具有显著的机械强度(P < 0.05)和高插入效率(F = 17.83, P = 3.03 × 10-8),并在30分钟内完全溶解于猪皮中。体外研究显示,液化天然气在48小时内持续释放(70.86 ± 0.42%),优于外用凝胶(42.33 ± 0.91%)。药物释放遵循一级动力学(R2 = 0.996)和非菲克扩散(n = 0.79),表明扩散-侵蚀联合机制。Wistar大鼠体内评估显示出显著的避孕效果,着床部位减少(0.5±0.55),子宫厚度减少(3.66±0.51 mm, p < 0.0001),与口服LNG相当。这些结果突出了LMNs作为长效透皮避孕的一个有前途的微创平台,提供了更好的生物利用度,患者依从性和治疗效果。
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来源期刊
CiteScore
9.10
自引率
0.00%
发文量
165
审稿时长
2 months
期刊介绍: Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs. Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.
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