Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.
Small. 2022 Oct;18(40):e2202156. doi: 10.1002/smll.202202156. Epub 2022 Sep 3.
The localization and accumulation of drugs in the body determine their therapeutic effects; however, the specific microstructure of damaged tissues hinders drug delivery. Currently, there is a shortage of effective drug carriers to breach these barriers and achieve efficient tissue and cellular delivery of drugs. In this study, an injectable double positively charged functional hydrogel microsphere with "targeting cartilage extracellular matrix", "cartilage penetration", and "cellular phagocytosis" is designed for matching the structural characteristics of joints, addressing the difficulties of drug delivery in joints. The microspheres could be adsorbed on the negatively charged cartilage surface because of their positively charged poly-lysine surface. Furthermore, the internally loaded positively charged polyamidoamine contained kartogenin, which helped further the penetration of the cartilage under the guidance of electrical charge. The microspheres could release kartogenin for more than 21 days. In in vivo experiments, the microspheres effectively improve the efficiency of drug delivery, inhibit the degradation of cartilage matrix and subchondral bone, and delay the development of osteoarthritis. As a double positively charged drug delivery system, the versatile microsphere has great potential for treating osteoarthritis and other diseases.
药物在体内的定位和积累决定了其治疗效果；然而，受损组织的具体微观结构阻碍了药物的传递。目前，缺乏有效的药物载体来突破这些障碍，实现药物在组织和细胞中的有效传递。在这项研究中，设计了一种可注射的双重正电荷功能水凝胶微球，具有“靶向软骨细胞外基质”、“软骨穿透”和“细胞吞噬”的功能，以匹配关节的结构特征，解决关节内药物传递的困难。由于微球表面带正电荷的聚赖氨酸，微球可以被带负电荷的软骨表面吸附。此外，内部负载的带正电荷的聚酰胺胺含有软骨素生成素，有助于在电荷的引导下进一步穿透软骨。微球可以释放软骨素生成素超过 21 天。在体内实验中，微球有效地提高了药物传递的效率，抑制了软骨基质和软骨下骨的降解，并延缓了骨关节炎的发展。作为一种双重正电荷药物传递系统，这种多功能微球在治疗骨关节炎和其他疾病方面具有巨大的潜力。
