Blanco Alfonso F, Lou Gustavo, Pensado-López Alba, Ummarino Aldo, Andón Fernando Torres, Crecente-Campo José, Alonso María José
Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain.
Drug Deliv Transl Res. 2025 Aug 25. doi: 10.1007/s13346-025-01942-5.
Knee osteoarthritis (OA), a degenerative joint disease, is increasingly prevalent worldwide and often results from a meniscal deterioration that leads to meniscus removal. Replacing the damaged meniscus with a non-biodegradable prosthesis offers an innovative solution to prevent OA progression, particularly in older patients. However, the long-term use of anti-inflammatory drugs for pain relief and prosthesis integration can cause severe off-target side effects. The objective of this work was to design and develop drug-loaded bilayer polymer films to be used as coatings for a meniscus polycarbonate urethane (PCU). The developed bilayer polymer films enabled a sustained release of two anti-inflammatory drugs - dexamethasone (DEX) and celecoxib (CLX) - with distinct release kinetics (1-4 weeks for DEX and 6-9 months for CLX). This release profile was defined to modulate post-surgical and chronic inflammation within the knee joint, respectively. Two bilayer prototypes showed consistent biodegradation, drug release, drug loading, and reproducibility. Furthermore, the systems were sterile, biocompatible, and maintained the anti-inflammatory efficacy of the released drugs, effectively reducing pro-inflammatory cytokine secretion from human primary macrophages.
膝骨关节炎（OA）是一种退行性关节疾病，在全球范围内日益普遍，通常由半月板退变导致半月板切除引起。用不可生物降解的假体替换受损半月板为预防OA进展提供了一种创新解决方案，尤其是在老年患者中。然而，长期使用抗炎药物来缓解疼痛和促进假体整合会导致严重的脱靶副作用。这项工作的目的是设计和开发载药双层聚合物薄膜，用作半月板聚碳酸酯聚氨酯（PCU）的涂层。所开发的双层聚合物薄膜能够持续释放两种抗炎药物——地塞米松（DEX）和塞来昔布（CLX），具有不同的释放动力学（DEX为1 - 4周，CLX为6 - 9个月）。这种释放模式分别被定义为调节膝关节手术后和慢性炎症。两种双层原型显示出一致的生物降解、药物释放、药物负载和可重复性。此外，该系统无菌、生物相容，并保持了所释放药物的抗炎功效，有效减少了人原代巨噬细胞分泌促炎细胞因子。
