Double-layered core-shell microneedle patch integrated with microparticles for long-acting treatment of osteoporosis

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.