Chitosan-Based Polyelectrolyte Complexes as Potential Nanoparticulate Carriers: Physicochemical and Biological Characterization

Title
Chitosan-Based Polyelectrolyte Complexes as Potential Nanoparticulate Carriers: Physicochemical and Biological Characterization
Author(s)
김종오용철순티르거네쉬라마사미트란탄힙조혁준김정환김용일전재윤[전재윤]최한곤[최한곤]
Keywords
DRUG-DELIVERY; IN-VITRO; BIOMEDICAL APPLICATIONS; HYBRID NANOPARTICLES; ACID NANOPARTICLES; ANTITUMOR-ACTIVITY; TARGETED DELIVERY; GENE DELIVERY; DOXORUBICIN; TRIPOLYPHOSPHATE
Issue Date
201405
Publisher
SPRINGER/PLENUM PUBLISHERS
Citation
PHARMACEUTICAL RESEARCH, v.31, no.5, pp.1302 - 1314
Abstract
To investigate the effect of polyelectrolytes on the formation and physicochemical properties of chitosan nanoparticles (CS-NPs) used for the delivery of an anticancer drug, doxorubicin (DOX). Three DOX-loaded CS-NPs were formulated with tripolyphosphate (CS-TP/DOX NPs), dextran sulfate (CS-DS/DOX NPs), and hyaluronic acid (CS-HA/DOX NPs) by using ionotropic gelation or complex coacervation. CS-TP/DOX NPs were the smallest, with an average size of 100 nm and a narrow size distribution, while CS-DS/DOX and CS-HA/DOX NPs were 200 nm in size. Transmission electron microscopy clearly showed a spherical shape for all the NPs. The strong binding affinity of DOX for the multiple sulfate groups in DS resulted in a sustained release profile from CS-DS/DOX NPs at pH 7.4, while CS-HA/DOX NPs exhibited faster DOX release. This trend was also present under acidic conditions, where release of DOX was significantly augmented because of polymer protonation. Compared to CS-TP/DOX or CS-DS/DOX NPs, CS-HA/DOX NPs showed superior cellular uptake and cytotoxicity in MCF-7 and A-549 cells, because of their ability to undergo CD44-mediated endocytosis. Pharmacokinetic studies clearly showed that all CS-NPs tested significantly improved DOX plasma circulation time and decreased its elimination rate constant. Consistent with the in vitro release data, CS-DS/DOX NPs exhibited a relatively better DOX plasma profile and enhanced blood circulation, compared to CS-HA/DOX or CS-TP/DOX NPs. Overall, these results demonstrated how NP design can influence their function. Taken together, CS-based polyelectrolyte complexes could provide a versatile delivery system with enormous potential in the pharmaceutical and biomedical sectors.
URI
http://hdl.handle.net/YU.REPOSITORY/32297http://dx.doi.org/10.1007/s11095-013-1251-9
ISSN
0724-8741
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약학대학 > 약학부 > Articles
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