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Exploring the translational potential of PLGA nanoparticles for intra-articular rapamycin delivery in osteoarthritis
Jian-Chao Ma1, Tingting Luo1, Binyang Feng1
1Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Abstract:
Osteoarthritis (OA) is a prevalent joint disease that affects all the tissues within the joint and currently lacks disease-modifying treatments in clinical practice. Despite the potential of rapamycin for OA disease alleviation, its clinical application is hindered by the challenge of achieving therapeutic concentrations, which necessitates multiple injections per week. To address this issue, rapamycin was loaded into poly(lactic-co-glycolic acid) nanoparticles (RNPs), which are nontoxic, have a high encapsulation efficiency and exhibit sustained release properties for OA treatment. The RNPs were found to promote chondrogenic differentiation of ATDC5 cells and prevent senescence caused by oxidative stress in primary mouse articular chondrocytes. Moreover, RNPs were capable to alleviate metabolism homeostatic imbalance of primary mouse articular chondrocytes in both monolayer and 3D cultures under inflammatory or oxidative stress. In the mouse destabilization of the medial meniscus (DMM) model, intra-articular injection of RNPs effectively mitigated joint cartilage destruction, osteophyte formation, chondrocytes hypertrophy, synovial inflammation, and pain. Our study demonstrates the feasibility of using RNPs as a potential clinically translational therapy to prevent the progression of post-traumatic OA.
Insights
Rapamycin-loaded nanoparticles (RNPs) offer a promising treatment for osteoarthritis (OA), reducing joint damage and inflammation. This sustained-release therapy overcomes challenges of frequent injections, potentially preventing OA progression.
Area of Science:
- Biomedical Engineering
- Nanotechnology in Medicine
- Osteoarthritis Research
Background:
- Osteoarthritis (OA) is a widespread degenerative joint disease with no current disease-modifying treatments.
- Rapamycin shows potential for OA treatment, but clinical use is limited by the need for frequent injections to maintain therapeutic levels.
Purpose of the Study:
- To develop and evaluate rapamycin-loaded poly(lactic-co-glycolic acid) nanoparticles (RNPs) for sustained OA treatment.
- To assess the efficacy of RNPs in preventing OA progression in vitro and in vivo.
Main Methods:
- Rapamycin was encapsulated into poly(lactic-co-glycolic acid) nanoparticles (RNPs) with high efficiency and sustained release.
- In vitro studies assessed RNP effects on chondrogenic differentiation and oxidative stress-induced senescence in ATDC5 cells and primary mouse articular chondrocytes.
- In vivo efficacy was evaluated using the destabilization of the medial meniscus (DMM) mouse model of post-traumatic OA.
Main Results:
- RNPs promoted chondrogenic differentiation and prevented oxidative stress-induced senescence in chondrocytes.
- RNPs alleviated metabolic imbalances in chondrocytes under inflammatory and oxidative stress conditions.
- Intra-articular RNP injection in DMM mice significantly reduced cartilage destruction, osteophyte formation, chondrocyte hypertrophy, synovial inflammation, and pain.
Conclusions:
- Rapamycin-loaded nanoparticles (RNPs) provide a viable, sustained-release drug delivery system for osteoarthritis.
- RNPs demonstrate therapeutic potential by protecting chondrocytes and mitigating key OA pathologies in a preclinical model.
- RNPs represent a clinically translatable therapy for preventing post-traumatic osteoarthritis progression.
