Intra-Articular Injection of PLGA/Polydopamine Core–Shell Nanoparticle Attenuates Osteoarthritis Progression

Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degeneration. Unfortunately, currently available clinical drugs are mainly analgesics and cannot alleviate the development of OA. Kartogenin (KGN) has been found to promote the differentiation of bone marrow mesench...

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Published in:ACS applied materials & interfaces 2024-05, Vol.16 (17), p.21450-21462
Main Authors: Zong, Lujie, Wang, Qing, Sun, Houyi, Wu, Qian, Xu, Yaozeng, Yang, Huilin, Lv, Shujun, Zhang, Liang, Geng, Dechun
Format: Article
Language:English
Subjects:
Anilides
Animals
Biological and Medical Applications of Materials and Interfaces
Drug Carriers - chemistry
Humans
Indoles - chemistry
Indoles - pharmacology
Injections, Intra-Articular
Male
Mesenchymal Stem Cells - drug effects
Mesenchymal Stem Cells - metabolism
Nanoparticles - chemistry
Osteoarthritis - drug therapy
Osteoarthritis - pathology
Phthalic Acids - chemistry
Phthalic Acids - pharmacology
Polylactic Acid-Polyglycolic Acid Copolymer - chemistry
Polymers - chemistry
Rats
Rats, Sprague-Dawley
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Summary:Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degeneration. Unfortunately, currently available clinical drugs are mainly analgesics and cannot alleviate the development of OA. Kartogenin (KGN) has been found to promote the differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocytes for the treatment of cartilage damage in early OA. However, KGN, as a small hydrophobic molecule, is rapidly cleared from the synovial fluid after intra-articular injection. This study synthesized a KGN-loaded nanocarrier based on PLGA/polydopamine core/shell structure to treat OA. The fluorescence signal of KGN@PLGA/PDA-PEG-E7 nanoparticles lasted for 4 weeks, ensuring long-term sustained release of KGN from a single intra-articular injection. In addition, the polyphenolic structure of PDA enables it to effectively scavenge reactive oxygen species, and the BMSC-targeting peptide E7 (EPLQLKM) endows KGN@PLGA/PDA-PEG-E7 NPs with an effective affinity for BMSCs. As a result, the KGN@PLGA/PDA-PEG-E7 nanoparticles could effectively induce cartilage in vitro and protect the cartilage and subchondral bone in a rat ACLT model. This therapeutic strategy could also be extended to the delivery of other drugs, targeting other tissues to treat joint diseases.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.3c18464