Exploring the translational potential of PLGA nanoparticles for intra-articular rapamycin delivery in osteoarthritis therapy

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. Graphical abstract

Functional Nanomaterials for the Treatment of Osteoarthritis

“…RNPs reduced the need for multiple injections, promoted chondrogenic cell differentiation in ATDC5 cells, and prevented oxidative stress-induced senescence in articular chondrocytes. 65 Sohn et al also showed that RAP lipid NPs induce immunomodulation of type II collagen in joints and alleviate OA by suppressing inflammation. 85

Figure 3 ( A ) Diagram illustrating the active loading of meloxicam liposomes (MLX-Ca(AC) 2Lipo) and its key benefits over passive loading methods, including efficient drug encapsulation, secure drug storage, and controlled drug release.

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“…PNPs are versatile for drug delivery, as drugs can be encapsulated within nanomaterials and polymer molecules, chemically bound to polymers, or bound to the surface of nanomaterials. 65 Thus, compounds, both hydrophobic and hydrophilic in nature, together with drugs of varying molecular weights, can be delivered via them. 66 Synthetic polymer NPs offer advantages such as good biocompatibility, controlled release, and high drug-carrying capacity, but they also face challenges with degradation rate, stability, and safety.…”

Nanotechnology’s frontier in combatting infectious and inflammatory diseases: prevention and treatment

“…Complex approval processes for new materials may prolong the time to clinical translation, as the safety and efficacy of NPs must undergo rigorous review. 679 , 680 Criteria for review include NP characterization and toxicity, where characterization would include size, shape, surface charge, stability, etc. In addition, unlike the singularity of preclinical research, clinical translation requires the cooperation of multiple departments, such as R&D institutions, experimental centers, regulatory agencies, and financial support.…”

Integrated Network Pharmacology and Experimental Validation Approach to Investigate the Mechanisms of Radix Rehmanniae Praeparata - Angelica Sinensis - Radix Achyranthis Bidentatae in Treating Knee Osteoarthritis

“… 17 Stressful conditions such as inflammation or elevated ROS levels cause chondrocyte anabolism to decrease, while catabolism increases, hastening the onset of OA. 18 As translational therapeutics, multifaceted techniques, such as ROS clearance and inflammation reduction under stressful conditions, show promise. 19 , 20 …”

“…17 Stressful conditions such as inflammation or elevated ROS levels cause chondrocyte anabolism to decrease, while catabolism increases, hastening the onset of OA. 18 As translational therapeutics, multifaceted techniques, such as ROS clearance and inflammation reduction under stressful conditions, show promise. 19,20 Herbal pharmaceutically active components, which have comprehensive therapeutic effects and few side effects on the human body, have particular effects and great development potential for lowering oxidative stress and treating KOA.…”