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

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

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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）是关节炎的最常见形式，影响了超过3250万的美国成年人相关的医疗保健每年的成本超过1850亿美元。目前的骨关节炎地址治疗疾病调整潜力有限的症状。炎症是关节OA的关键介体，使其成为骨关节炎治疗的关键靶点。但是，可用的抗炎药（例如类固醇）迅速从关节清除。富勒烯（C60）具有有效的抗炎作用，本质上优于类固醇和其他分子由于其长期活性和细胞膜渗透能力而引起的。我们最近开发了一种能够抑制炎症和靶向的纳米板cflflf-C60 巨噬细胞，增强持续的关节保留和治疗作用。这个项目的目标是确定纳米文化对OA和相关疼痛的治疗功效。 AIM 1将评估 CFLFLF-C60在炎症OA的人植体模型中的功效。它将确定CFLFLF-C60是否抑制人类关节外植体的软骨降解和炎症。 AIM 2将确定治疗小鼠模型中的OA和相关疼痛。它将阐明CFLFLF-C60的功效和时间窗口修改软骨变性和疼痛。该项目代表了该领域的新方向因为它解决了OA的潜在发病机理和持续的关节输送。