Chitosan-based polyelectrolyte complexes as potential nanoparticulate carriers: physicochemical and biological characterization.
Pharm Res
; 31(5): 1302-14, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24297070
ABSTRACT
PURPOSE:
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).METHOD:
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.RESULTS:
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.CONCLUSIONS:
Taken together, CS-based polyelectrolyte complexes could provide a versatile delivery system with enormous potential in the pharmaceutical and biomedical sectors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Portadores de Fármacos
/
Quitosana
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Eletrólitos
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Nanopartículas
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Coréia do Sul