Novel protein-loaded chondroitin sulfate–chitosan nanoparticles: Preparation and characterization

• Published in: Acta biomaterialia Vol. 7; no. 10; pp. 3804 - 3812
• Main Authors: Yeh, Ming-kung, Cheng, Kuang-ming, Hu, Chieh-shen, Huang, Yu-chuan, Young, Jenn-jong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2011
• Subjects: Animals; bovine serum albumin; Caco-2 Cells; Cattle; Cell Death - drug effects; Cell Survival - drug effects; Cell uptake; Chitosan; Chitosan - chemical synthesis; Chitosan - pharmacology; Chondroitin sulfate; Chondroitin Sulfates - chemical synthesis; Chondroitin Sulfates - pharmacology; crosslinking; Cytotoxicity; drugs; encapsulation; fluorescein; Fluorescein-5-isothiocyanate - analogs & derivatives; Fluorescein-5-isothiocyanate - chemistry; gravimetry; HEK293 Cells; human cell lines; Humans; Hydrogen-Ion Concentration - drug effects; hydrophilicity; Kinetics; Microscopy, Confocal; Molecular Weight; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Particle Size; Serum Albumin, Bovine - chemistry; Serum Albumin, Bovine - ultrastructure; sodium tripolyphosphate; Spectroscopy, Fourier Transform Infrared; Static Electricity; Water - chemistry; water content; zeta potential; Nanoparticles; Cell uptake; Cytotoxicity; Chondroitin sulfate; Chitosan
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2011.06.026

In this study, the potential of chondroitin sulfate (ChS)–chitosan (CS) nanoparticles (NPs) for the delivery of proteins was investigated. ChS–CS NPs were prepared by ionic cross-linking of CS solution with ChS. The aggregation line, particle size and zeta potential were investigated as a function of the pH, weight ratio and concentration. The water content and formation yield of the NPs were measured by gravimetry. Results indicated that ChS–CS NPs showed a higher degree of ionic cross-linking and formation yield than sodium tripolyphosphate–CS NPs. Fluorescein isothiocyanate conjugate bovine serum albumin (FITC–BSA), a model protein drug, was incorporated into the ChS–CS NPs. The encapsulation efficiency was obviously increased with the increase in initial FITC–BSA concentration and was as high as 90%. In vitro release studies of ChS–CS NPs showed a small burst effect following a continued and controlled release. Cytotoxicity tests with Caco-2 cells showed no toxic effects of ChS–CS NPs. The ex vivo cellular uptake studies using Caco-2 and HEK-293 cells indicated that NPs were found to be endocytosed into the cells. In conclusion, ChS–CS NPs are a potential new delivery system for the transport of hydrophilic compounds such as proteins.