Chondroprotective Effects of Chitosan‐Coated Poly(Lactic‐<i>co</i>‐Glycolic Acid) Nanocapsulized Curcumin on Human Articular Chondrocytes

Dysregulation of pro-inflammatory cytokines participates in the initiation and development of knee osteoarthritis (OA). Consequently, interventions to boost the anti-inflammatory capacity of articular chondrocytes have been proposed to treat early-stage OA and prevent OA progression. Applying nanoencapsulation can enhance bioavailability and bioactivity and sustain the anti-inflammatory activity of phytochemicals. Accordingly, in this study, we used nanocapsules to deliver curcumin (Cur) to treat inflammatory chondrocytes. Using double-emulsion technology, Cur was encapsulated in chitosan-coated poly(lactic-co-glycolic acid) nanocapsules. The nanocapsulized Cur (NCcur) was characterized, and the toxicity to human articular chondrocytes was evaluated. NCcur was applied to interleukin-1 beta (IL-1β)-stimulated cells based on findings of the Cur toxicity study. Results showed that the particle size of NCcur was 247.8 ± 1.73 nm with a zeta potential of 20.3 ± 0.11 mV and a mid-range distribution. NCcur showed a core-shell and sphere-like morphology. The encapsulation efficiency of Cur in nanocapsules was 67.1%. Nanoencapsulation decreased the toxicity of high-dose Cur (> 20 μM), and NCcur exhibited a sustained Cur release over 72 h. NCcur supplementation (20 μM) improved cell survival and ameliorated cell senescence of inflammatory chondrocytes. The IL-1β-induced IL1B, IL6, metalloproteinase-9 (MMP9), and MMP13 mRNA expressions were down-regulated, while IL10 level was enhanced in NCcur-treated chondrocytes. Likewise, NCcur supplementation restored aggrecan, collagen type II alpha 1 chain, and SOX9 mRNA expressions. MMP-13, IL-8, and MCP-1 secretions in the supernatant also decreased. By applying nanocapsules, we assumed the anti-inflammatory capacity of Cur could be sustained for treating knee OA.