Xu Bo, Zhang Suohui, Liu Han, Yang Guozhong, Zhou Zequan, Gao Yunhua
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China; Beijing CAS Microneedle Technology Ltd., Beijing 102609, China.
J Control Release. 2025 Aug 10;384:113898. doi: 10.1016/j.jconrel.2025.113898. Epub 2025 May 29.
Osteoporosis is one of the most common diseases affecting the elderly, particularly postmenopausal women. It significantly increases the risk of fractures, reduces quality of life, and adds to the medical burden. Traditional formulations, such as alfacalcidol (ALF) capsules and tablets, have limitations, including difficulties in swallowing and patient resistance to long-term medication use, highlighting the urgent need for a sustained-release ALF formulation. To address this, we developed a double-layered core-shell microneedle patch integrated with ALF-loaded microparticles for the long-acting treatment of osteoporosis. This system aims to reduce administration frequency and improve patient compliance. After application for just 5 min, the patch can be removed, leaving the microneedle tips embedded in the skin. The core-shell structure of the tip consists of a core made of ALF-loaded polylactic-co-glycolic acid (PLGA) microparticles and a shell composed of ethylcellulose (EC). This structure acts as a drug reservoir within the skin, enabling for sustained release of ALF over 14 days. Compared to commercially available ALF tablets which require daily administration, the long-acting ALF double-layered core-shell microneedle patch (ALF-DCSMN) delivers a lower systemic drug dose while demonstrating comparable or better efficacy in increasing bone mass and improving trabecular microstructure. Notably, ALF-DCSMN only requires semimonthly administration. Overall, these promising results suggest that the ALF-DCSMN is a safe, effective, and user-friendly transdermal formulation for the long-acting treatment of osteoporosis.
骨质疏松症是影响老年人，尤其是绝经后女性的最常见疾病之一。它显著增加了骨折风险，降低了生活质量，并加重了医疗负担。传统剂型，如阿法骨化醇（ALF）胶囊和片剂，存在局限性，包括吞咽困难以及患者对长期用药的抵触情绪，这凸显了对阿法骨化醇缓释制剂的迫切需求。为解决这一问题，我们开发了一种双层核壳微针贴片，集成了负载阿法骨化醇的微粒，用于骨质疏松症的长效治疗。该系统旨在减少给药频率并提高患者依从性。贴片仅需贴敷5分钟即可移除，微针尖端则留在皮肤中。尖端的核壳结构由负载阿法骨化醇的聚乳酸-乙醇酸共聚物（PLGA）微粒制成的内核和由乙基纤维素（EC）组成的外壳构成。这种结构在皮肤内充当药物储存库，使阿法骨化醇能够持续释放14天。与需要每日给药的市售阿法骨化醇片剂相比，长效阿法骨化醇双层核壳微针贴片（ALF-DCSMN）在增加骨量和改善小梁微结构方面，全身药物剂量更低，同时显示出相当或更好的疗效。值得注意的是，ALF-DCSMN仅需半月给药一次。总体而言，这些令人鼓舞的结果表明，ALF-DCSMN是一种安全、有效且用户友好的经皮制剂，用于骨质疏松症的长效治疗。
