Macrophage Anchoring Nanomedicine to Replace Steroids for Intra-articular Injection

点击翻译按钮获取中文摘要

Osteoarthritis (OA) is the most common form of arthritis, affecting more than 32.5 million of US adults, with an associated healthcare cost at more than $185 billion annually. Current treatments for osteoarthritis address symptoms with limited disease-modifying potential. Inflammation is the key mediator of joint OA, making it the key target for osteoarthritis treatment. However, available anti-inflammatory drugs, such as steroids, are rapidly cleared from the joint. Fullerenes (C60) possess potent anti-inflammatory effects and are intrinsically superior to steroids and other molecules due to their long-lasting activity and cell membrane-penetrating capability. We recently developed a nanoplatform cFLFLF-C60 capable of suppressing inflammation and targeting macrophages, potentiating sustained joint retention and therapeutic effects. The goal of this project is to determine the therapeutic efficacy of the nanoplatform on OA and associated pain. Aim 1 will evaluate the efficacy of cFLFLF-C60 in human explant models of inflammatory OA. It will establish whether cFLFLF-C60 inhibits cartilage degradation and inflammation in human joint explants. Aim 2 will determine the sustained effects of treating OA and associated pain in a mouse model. It will elucidate the efficacy and time window of cFLFLF-C60 to modify cartilage degeneration and pain. This project represents a new and distinct direction for the field because it addresses the underlying pathogenesis of OA and sustained joint delivery.