Lin Guangyong, Huang Huirong, Sun Meng, He Zhinan, Li Shengjie, Liang Xindan, Yan Yuqi, Qiu Chenyu, Li Shize, Zhao Xinyu, Zhu Wanling, Kou Longfa, Chen Ruijie
Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, China.
Mater Today Bio. 2024 Sep 28;29:101279. doi: 10.1016/j.mtbio.2024.101279. eCollection 2024 Dec.
Osteoarthritis (OA) remains a challenging degenerative joint disease, largely associated with chondrocyte apoptosis during its development. Preserving chondrocytes stands as a promising strategy for OA treatment. Rapamycin (RP) exhibits chondrocyte protection by fostering autophagy. Nevertheless, the swift clearance of intra-articular injections and the dense cartilage extracellular matrix (ECM) hinder RP from effectively reaching chondrocytes. Herein, we developed a "two-stage" drug delivery system (RP@PEG-PA@P-Lipo). This system comprises primary nanoparticles (P-Lipo), liposomes modified with a collagen II targeting peptide (WYRGRLC), and secondary nanoparticles (RP@PEG-PA), PEG-modified PAMAM encapsulating rapamycin (RP). RP@PEG-PA@P-Lipo demonstrates adherence to the cartilage surface with WYRGRLC, substantially prolonging retention within the joint cavity. Subsequently, released RP@PEG-PA can effectively penetrate the cartilage and deliver RP to chondrocytes through small size and charge-driven forces. and experiments corroborate its notable therapeutic effects on OA. This study holds promise in offering a novel approach for clinical drug delivery and OA treatment.
骨关节炎（OA）仍然是一种具有挑战性的退行性关节疾病，在其发展过程中很大程度上与软骨细胞凋亡有关。保护软骨细胞是一种有前景的OA治疗策略。雷帕霉素（RP）通过促进自噬表现出软骨细胞保护作用。然而，关节内注射药物的快速清除以及致密的软骨细胞外基质（ECM）阻碍了RP有效到达软骨细胞。在此，我们开发了一种“两阶段”药物递送系统（RP@PEG-PA@P-Lipo）。该系统包括初级纳米颗粒（P-Lipo），即经II型胶原蛋白靶向肽（WYRGRLC）修饰的脂质体，以及次级纳米颗粒（RP@PEG-PA），即包裹雷帕霉素（RP）的聚乙二醇修饰的聚酰胺-胺。RP@PEG-PA@P-Lipo通过WYRGRLC表现出对软骨表面的粘附性，大大延长了在关节腔内的保留时间。随后，释放的RP@PEG-PA可通过小尺寸和电荷驱动力有效穿透软骨并将RP递送至软骨细胞。 实验证实了其对OA具有显著的治疗效果。本研究有望为临床药物递送和OA治疗提供一种新方法。
