Affiliation:
1. Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road Shanghai 200025 P. R. China
2. Department of Orthopedics The First Affiliated Hospital of Chongqing Medical University Orthopedic Laboratory of Chongqing Medical University Chongqing 400016 P. R. China
Abstract
AbstractThe high density structure of cartilage matrix negative charge seriously hinders the penetration and enrichment of drugs/genes into cartilage tissue. In this study, hexachlorocyclotriphosphonitrile is used as the core to prepare self‐polymerized phosphorus dendrimers with inflammatory reaction through substitution and condensation reaction. The vector can achieve efficient penetration of the damaged articular cartilage (slightly acidic condition) and effective anchoring of cartilage matrix (normal physiological condition) through the size effect under inflammatory response. Meanwhile, as a gene “delivery library,” G1‐NC5.HCl@siRNA is gradually released with microspheres degrading; the long‐term silencing of specific genes is realized. Further, G1‐NC5.HCl@siRNA is loaded into the hydrogel microspheres by ionic bond coordination and microfluidic techniques to improve the residency effect of G1‐NC5.HCl@siRNA in the joint cavity. The results of cartilage in vitro and in vivo experiments show that the gene complex has a better penetration effect at pH = 6.6, and the cartilage penetration effect decreases at pH = 7.6, which can effectively anchor in the cartilage matrix site for continuous drug delivery. Further, the composite hydrogel microspheres significantly improve the degeneration of osteoarthritis (OA) cartilage and promote cartilage regeneration. Therefore, the self‐polymerized hydrogel microsphere delivery system with inflammatory response is a promising penetrant/anchoring carrier system for OA treatment.
Funder
National Key Research and Development Program of China
China Postdoctoral Science Foundation
Shanghai Municipal Health and Family Planning Commission
Subject
Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials
Cited by
1 articles.
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