Abstract
Poly(D,L-lactide-co-glycolide) nanoparticles (PLGA NPs) modified with chitosan (CS) have been used as carriers for epirubicin (EPB) to overcome multidrug resistance in an adriamycin-resistant human breast cancer cell line (MCF-7/ADM). EPB-loaded PLGA NPs were prepared using the solvent evaporation technique and then surface modified with CS according to the adsorption (ADCS NPs) and chemical binding methods (CBCS NPs). The EPB-loaded PLGA NPs were observed to be spherical in shape by scanning electron microscopy and their mean size was determined to be 214.4 ± 21.0 by laser light scattering. The size of the EPB-loaded PLGA NPs increased following the CS-surface modification, but the drug encapsulation efficiency was reduced from 84.1 ± 3.4 to 72.0 ± 3.5% for the ADCS NPs and to 70.1 ± 3.6% for the CBCS NPs. The rates of in vitro drug release from the CS-modified NP formulations were determined by dialysis with both systems showing a biphasic release pattern involving an initial rapid release followed by a very slow release after 24 h. Moreover, the results of cell experiments showed that the cellular uptake of the CS-modified NPs into the MCF-7/ADM cells had increased compared with the free EPB and EPB-loaded PLGA NP, whereas their inhibitory effects on cell viability were reduced. Taken together, these results demonstrate that CS-modified EPB-loaded PLGA NPs exhibit several advantages for sustained drug release and the enhancement of drug toxicity in drug-resistant tumor cells, indicating that NPs of this type could potentially be used as carriers for anticancer drugs.
Keywords: Anticancer activity, chitosan, epirubicin hydrochloride, modification, PLGA nanoparticles.
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