Disulphide cross linked pullulan based cationic polymer for improved gene delivery and efflux pump inhibition
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Date
2016
Journal Title
Journal ISSN
Volume Title
Publisher
COLLOIDS AND SURFACES B-BIOINTERFACES
Abstract
Multidrug resistance is a hurdle to successful cancer chemotherapy. Over expression of P-glycoprotein (P-gp) is a prime contributing factor for drug resistance. In this study, a disulphide cross-linked pullulan-based cationic polymer (PPSS) was synthesized to act simultaneously as gene delivery vehicle and efflux pump inhibitor. The PPSS nanoplexes were of size <200 nm with the zeta potential of +15 to +20 mV. The cytotoxicity studies using C6 and L929 cells showed that PPSS polymers are non-toxic even at high polymer concentrations. The PPSS/pDNA nanoplex showed superior uptake in confocal microscopy with 97% uptake by flow cytometry. The efficacy of efflux pump inhibition by the PPSS nanoplex was established by the enhanced intracellular retention of DOX. The enhanced cell death by p53/PPSS/DOX nanoplexes was attributed to the synergistic effect of P-gp inhibition and p53 transfection efficiency. Therefore, this multifunctional polymeric system may have significant promise for therapeutic application against cancer drug resistance. (C) 2016 Elsevier B.V. All rights reserved.
Description
Keywords
Biophysics; Chemistry; Materials Science
Citation
146 ,;879-887