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Macrophage Anchoring Nanomedicine to Replace Steroids for Intra-articular Injection

巨噬细胞锚定纳米药物替代类固醇用于关节内注射

基本信息

批准号：
10574148
负责人：
Li Jin
金额：
$ 17.77万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-15 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10574148
关键词：
Address Adult Affect Animals Anti-Inflammatory Agents Antiinflammatory Effect Arthritis Binding Cartilage Cartilage Matrix Cell membrane Charge Chondrocytes Confocal Microscopy Degenerative polyarthritis Disease Dose Drug or chemical Tissue Distribution Drug usage Electrostatics Evaluation FPR1 gene Free Radical Scavenging Fullerenes Goals Growth Factor Harvest Health Care Costs Histology Human Hyaluronic Acid Infiltration Inflammation Inflammation Mediators Inflammatory Injections Injury Interleukin-1 beta Intra-Articular Injections Joints Knee Knee Osteoarthritis Knee joint Macrophage Measures Mechanics Medial meniscus structure Mediator Modality Modeling Monitor Mus Musculoskeletal Diseases Neuropeptides Nociception Outcomes Research Pain Pathogenesis Pathology Penetration Peptides Permeability Persons Pharmaceutical Preparations Phenotype Property Research Spinal Ganglia Steroids Surface Symptoms Synovial Membrane Therapeutic Effect Time Tissue Harvesting Tissues Translations Treatment Efficacy cartilage degradation chondroprotection clinical translation clinically relevant clinically significant confocal imaging efficacy evaluation experimental study fullerene C60 in vivo in vivo imaging system injured joint destruction joint inflammation joint injury knee pain microCT mouse model multiplex assay nanomedicine nanoparticle nanotechnology platform novel prevent receptor regenerative synthetic peptide therapeutic target uptake

项目摘要

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.

骨关节炎（OA）是最常见的关节炎形式，影响着超过3250万美国成年人