Permana Andi Dian, Aziz Anugerah Yaumil Ramadhani, Ilyas Nur Rezky Aulia, Putri Aprilia Paramitha Dwi, Domìnguez-Robles Juan, Asri Rangga Meidianto, Amir Muhammad Nur, Fauziah Nurul, Chabib Lutfi, Febrian Muhammad Pandoman
Department of Pharmaceutical Science and Technology, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia.
Department of Pharmaceutical Science and Technology, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia.
Int J Pharm. 2025 Jan 25;669:125085. doi: 10.1016/j.ijpharm.2024.125085. Epub 2024 Dec 12.
The increasing prevalence of unintended pregnancies, a persistent issue affecting public health and hindering progress towards the Sustainable Development Goals (SDGs), highlights the critical need for innovative contraceptive approaches. While current methods, including hormonal contraceptives such as levonorgestrel (LNG), offer potential solutions, challenges like limited access and inconsistent use persist. This study introduces a new approach with the development of a three-layer microneedle (TIMN) containing LNG designed to provide extended contraceptive efficacy. The TIMN was formulated with varying concentrations of polyvinylpyrrolidone (PVP) and polycaprolactone (PCL) in the first layer, resulting in microneedles approximately 700 µm in height. In this study, TIMN demonstrated superior mechanical strength with less than 10% reduction in needle height under compression. The formulations maintained a surface pH within the skin's normal range, ensuring safety and compatibility, while water vapor transmission (WVT) values indicated good stability under high humidity. Moisture absorption ability (MAA) testing showed low water absorption, suggesting suitability for extended use. In vitro release studies revealed that TIMN released 28.34% of LNG after 24 h and up to 97.34% over 14 days, demonstrating controlled and sustained release. Ex vivo studies confirmed TIMN's longer-lasting LNG availability compared to the control, and in vivo pharmacokinetic studies showed that TIMN maintained therapeutic LNG levels for up to 14 days, outperforming oral LNG suspension. Biocompatibility tests, including HET-CAM and hemolysis assays, confirmed TIMN's safety, with no significant irritation or toxicity. Histopathological analysis further supported the absence of adverse reactions. The TIMN formulation, exhibits promising properties for long-term drug delivery, including mechanical strength, stability, controlled release, and biocompatibility, making it a viable candidate for improved contraceptive therapy.
意外怀孕的患病率不断上升，这一长期存在的问题影响着公众健康并阻碍可持续发展目标（SDGs）的进展，凸显了对创新避孕方法的迫切需求。虽然当前的方法，包括左炔诺孕酮（LNG）等激素避孕药，提供了潜在的解决方案，但诸如获取受限和使用不一致等挑战依然存在。本研究引入了一种新方法，即开发一种含LNG的三层微针（TIMN），旨在提供长效避孕效果。TIMN的第一层采用了不同浓度的聚乙烯吡咯烷酮（PVP）和聚己内酯（PCL）进行配制，制成的微针高度约为700微米。在本研究中，TIMN表现出卓越的机械强度，在压缩下针高降低不到10%。这些制剂将表面pH维持在皮肤的正常范围内，确保了安全性和兼容性，而水汽透过率（WVT）值表明在高湿度下具有良好的稳定性。吸湿能力（MAA）测试显示吸水率低，表明适合长期使用。体外释放研究表明，TIMN在24小时后释放了28.34%的LNG，在14天内释放量高达97.34%，显示出可控的持续释放。离体研究证实，与对照组相比，TIMN的LNG可用性持续时间更长，体内药代动力学研究表明，TIMN可将治疗性LNG水平维持长达14天，优于口服LNG混悬液。包括鸡胚绒毛尿囊膜（HET-CAM）和溶血试验在内的生物相容性测试证实了TIMN的安全性，无明显刺激或毒性。组织病理学分析进一步支持了无不良反应。TIMN制剂在长期药物递送方面表现出有前景的特性，包括机械强度、稳定性、控释和生物相容性，使其成为改进避孕疗法的可行候选者。
