ROS-Sensitive Nanoparticles Co-delivering Dexamethasone and CDMP-1 for the Treatment of Osteoarthritis Through Chondrogenic Differentiation Induction and Inflammation Inhibition.

Xiaodong Wu,Weiling Huo,Pengpeng Li,Beiji Lu,Qiang Xu,Jian Cheng,Conghui Han

doi:10.3389/fbioe.2021.608150

Abstract

Objective: Osteoarthritis (OA) is a common subtype of arthritis. To date, treatment of OA focuses primarily on alleviating pain and improving joint function. The lack of a vascular system within synovial joints and the rapid removal of agents due to synovial exchange hinder continuous delivery of OA drugs. However, these obstacles are being addressed by promising nanoscale drugs.Methods: We synthesize and assemble a hydrogen peroxide [H2O2, belongs to the category of active oxygen species (ROS)]-sensitive nanomicelle, which is loaded with the anti-inflammation drug dexamethasone and chondrogenic differentiation factor cartilage-derivedmor-phogeneticprotein-1. The micelle can induce bone marrow mesenchymal stem cells to repair cartilage while inhibiting joint inflammation.Results: The prepared nanoparticles were of uniform size and displayed an obvious core-shell structure. Under H2O2 stimulation, the shell layer could be removed gradually. The drug-loaded micelle effectively inhibited proliferation of activated macrophages, induced macrophage apoptosis with an anti-inflammatory effect, and caused the BMSCs to differentiate into chondrocytes.Conclusion: This work provides an experimental and theoretical basis for further development of a drug-loaded micelle in the healing of osteoarthritis.

Highlights

Osteoarthritis (OA), a degenerative form of arthritis, causes articular cartilage damage and affects entire joints (Miller et al, 2019; Hunt et al, 2020)
Instruments The techniques used in this study included high-performance liquid chromatography (HPLC, Dionex UltiMate 3000, ThermoFisher), transmission electron microscopy (TEM, Hitachi, H-600), fluorescence microscopy (Zeiss 710, Jena, Germany), dynamic light scattering (DLS, Santa Barbara, Nicomp 380 ZLS), laser scanning confocal microscopy (Zeiss 710, Germany) and flow cytometry (BD Biosciences, BD FACS Canto II)
As shown in the DLS results (Figure 2A), the particle-size distribution of blank and drug-loaded nanoparticles displayed an obvious single-peak normal distribution, without trailing tail or double peak, which indicated that the sizes of the micelles were relatively uniform

Summary

Introduction

Osteoarthritis (OA), a degenerative form of arthritis, causes articular cartilage damage and affects entire joints (Miller et al, 2019; Hunt et al, 2020). Several surgical procedures have been operated to repair cartilage, including micro fractures (Bergink et al, 2019), mosaics (Jordan et al, 2017) and autologous chondrocytes (Stoop et al, 2007), but long-term success has proved elusive. To meet clinical needs and achieve long-term efficacy, non-invasive therapies that promote cartilage regeneration and exert anti-inflammatory effects are being designed (Boulocher et al, 2007; Palmer et al, 2013). Glucocorticoids (Cooper et al, 2016; Zhou et al, 2019) are often used to relieve joint pain during inflammation, but they are only effective in the short term. Hyaluronic acid drugs are able to relieve the symptoms of various types of osteoarthritis, but they tend to rapidly exit the joint cavity and provide relief for no more than 1–3 months

Methods

Results

Conclusion