Qing Hu1,2, Qing Chen3, Xiuyun Yan1, Bomei Ding1, Dawei Chen1,3, Lifang Cheng1. 1. Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, PR China. 2. Department of Pharmaceutics, College of Pharmaceutical Sciences, Fujian Medical University, Fuzhou 350108, PR China. 3. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Abstract
AIM: To develop a nanocarrier for targeted delivery of agents to the cartilage. MATERIALS & METHODS: Chondrocyte affinity peptide modified PEGylated polyamidoamine conjugates (CAP-PEG-PAMAM) were prepared and rhodamine B isothiocyanate (RB) fluorophore was linked on them for comparative biological tracing and profiling. RESULTS: CAP4-PP-RB exhibited much more efficient cellular uptake in vitro than that of PEG-PAMAM-RB. Both the conjugates were likely internalized by chondrocytes via clathrin and caveolin co-mediated endocytosis, and delivered to lysosomes. In vivo imaging demonstrated the fluorescein-labeled nanocarrier was capable to persist in the joint cavity of rats for a prolonged time. Furthermore, the CAP4-PEG-PAMAM showed a good biocompatibility and enhanced penetration effects in vivo. CONCLUSION: CAP-PEG-PAMAM could be an effective nanocarrier for intra-articular delivery of agents to cartilage.
AIM: To develop a nanocarrier for targeted delivery of agents to the cartilage. MATERIALS & METHODS: Chondrocyte affinity peptide modified PEGylated polyamidoamine conjugates (CAP-PEG-PAMAM) were prepared and rhodamine B isothiocyanate (RB) fluorophore was linked on them for comparative biological tracing and profiling. RESULTS:CAP4-PP-RB exhibited much more efficient cellular uptake in vitro than that of PEG-PAMAM-RB. Both the conjugates were likely internalized by chondrocytes via clathrin and caveolin co-mediated endocytosis, and delivered to lysosomes. In vivo imaging demonstrated the fluorescein-labeled nanocarrier was capable to persist in the joint cavity of rats for a prolonged time. Furthermore, the CAP4-PEG-PAMAM showed a good biocompatibility and enhanced penetration effects in vivo. CONCLUSION:CAP-PEG-PAMAM could be an effective nanocarrier for intra-articular delivery of agents to cartilage.
Entities:
Keywords:
cartilage breakdown; cartilage-targeting; cellular uptake; chondrocyte affinity peptide; chondrocytes; in vivo imaging; intra-articular injection; osteoarthritis; polyamidoamine (PAMAM) dendrimer