Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 454, Issue 1, Pages 425-434Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2013.06.056
Keywords
Chitosan; Drug delivery; Nanoparticles; Protein
Categories
Funding
- Ministry of Science and Technology of China (973 Program) [2009CB930402, 2011CB932503]
- innovative team of Ministry of Education of China [IRT0911]
- National Natural Science Foundation of China (NSFC) [21274026, 20874016]
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A series of novel amphiphilic chitosan derivatives, cholic acid modified N-(2-hydroxy)-propyl-3-trimethylammonium chitosan chloride (HTCC-CA) with different quaternization degrees and cholic acid substitutions were synthesized in this study. HTCC-CA is biocompatible and forms particles in aqueous solution. The binding with superoxide dismutase (SOD) at pH 6.8 destroys the original aggregates of HTCC-CA and produces smaller SOD/HTCC-CA complex nanoparticles via electrostatic and hydrophobic interactions. The SOD loading efficiency and loading capacity of HTCC-CA can reach to more than 90% and 45%, respectively. Confocal laser scanning microscopy observation and flow cytometry analysis reveal that SOD/HTCC-CA complex nanoparticles greatly enhance the cellular internalization of the loaded SOD. The SOD activities and malonaldehyde concentrations in the serum and organs of the rats, administrated intravenously with free SOD, free HTCC-CA, and SOD/HTCC-CA nanoparticles, were assayed to evaluate the antioxidant efficiency in vivo. The results demonstrate that free HTCC-CA is effective to scavenge superoxide radicals in the blood circulation and SOD/HTCC-CA nanoparticles have better antioxidant efficiency than free SOD as well as free HTCC-CA. (C) 2013 Elsevier B.V. All rights reserved.
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