مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Anti-inflammatory and chondroprotective activity of a small-molecule-loaded nanoparticle/hydrogel system
Anti-inflammatory and chondroprotective activity of a small-molecule-loaded nanoparticle/hydrogel system
Zahra Nabizadeh,1,*Davood Nasrabadi,2
1. Neuroscience Research Center, Qom University of Medical Sciences, Qom, Iran 2. Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
Introduction: Cartilage lesions typically cause pain and disability, often necessitating medical intervention due to the inflammation at the damaged site and the cartilage tissue's limited self-healing capacity. This study aimed to develop a small-molecule-loaded nanoparticle hydrogel system with anti-inflammatory and chondroprotective properties for the treatment of OA.
Methods: Fisetin-loaded chitosan nanoparticles (FNPs) and KGN-loaded chitosan nanoparticles (K-CS NPs) were prepared using the absorption method and covalent attachment, respectively. Next, chitosan nanoparticles (CS NPs) loaded with small molecules (Fisetin and KGN) were incorporated into the injectable hyaluronan hydrogel to improve the release profile of the drug and increase its retention time in the joint cavity. Then, the IL-1β-stimulated chondrocytes were encapsulated in hyaluronan hydrogel containing FNPs and K-CS NPs, individually or in combination, to explore their potential chondroprotective and anti-inflammatory effects.
Results: FNPs and K-CS NPs showed sizes of 363.1 ± 17.2 and 232.7 ± 4.5 nm, respectively, suitable for intra-articular (IA) injection. Based on the hemolysis results, both drug-loaded CS NPs exhibited good hemocompatibility within the studied range. Adding drug-loaded CS NPs to hyaluronan hydrogel improved its drug release profile, swelling, and degradation. In addition, the real-time PCR results showed that the hyaluronan hydrogel containing both drug-loaded CS NPs performed better than either constituent alone on an in vitro model of OA.
Conclusion: In OA treatment, the therapeutic effects mainly depend on the retention time of the drug in the joint cavity. Therefore, injecting this nanoparticle hydrogel system into the knee cavity may improve drug bioavailability, rapidly suppress inflammation and pain, and promote cartilage regeneration. However, this system needs further investigation in an animal model of OA.