ArticleDrug design, development and therapy2026
Celecoxib-Loaded "Nano-in-Nano" Hierarchical Delivery System: Structure-Driven Synergistic Optimization of Diffusion Efficiency and Mechanical Stability for Osteoarthritis Therapy.
Article in Drug design, development and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: Osteoarthritis (OA) joints present abnormal mechanical environments that limit drug retention and therapeutic efficacy. Current intra-articular systems cannot provide both sustained anti-inflammatory delivery and mechanical support. A celecoxib (CXB)-loaded "Nano-in-Nano" Hierarchical Delivery System (NiN-HDS) was developed to simultaneously optimize drug release and joint reinforcement. Methods: In this study, celecoxib-loaded PLGA nanoparticles (CXB-NPs) were prepared by emulsion solvent evaporation and incorporated into an electrospun nanofiber membrane combined with a genipin-crosslinked gelatin layer to form NiN-HDS. The system was characterized for particle size, zeta potential, porosity, hydrophilicity, swelling, degradation, mechanical properties, and in vitro CXB release. Therapeutic potential was evaluated in a rat OA model using histological and immunohistochemical analyses of cartilage and inflammatory markers. Results: NiN-HDS maintained nanoparticle stability, with CXB-NPs showing an average particle size of 138.4 ± 4.3 nm and a zeta potential of -58.74 ± 16.58 mV. The system exhibited high porosity (87.16 ± 0.75%) and hydrophilicity (contact angle < 90°), achieved swelling equilibrium at 150 ± 10 min with a swelling ratio of 163.97 ± 9.76%, and degraded over 10 days with 88.53 ± 2.03% mass loss. Mechanical testing demonstrated high strength (Young's modulus 17.24 ± 2.65 MPa, elongation at break 307.48 ± 32.01%. NiN-HDS provided sustained CXB release over 7 days, reaching 67.16% cumulative release. In vivo, it reduced cartilage damage and suppressed IL-1β and MMP-13 expression, while maintaining mechanical support and controlled drug delivery. Conclusion: In conclusion, we successfully developed NiN-HDS. Our results show that NiN-HDS combines sustained drug delivery with mechanical support, improves cartilage preservation and reduces local inflammation in a rat OA model, indicating that it can serve as a promising strategy for intra-articular therapy of osteoarthritis.
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