Design and Characterization of Thermo and Ph Dual Responsive Polymeric Nanoparticles for Cancer Therapy

Abstract

Background: Oxaliplatin (OXA) is third generation platinum based antitumor drug newlinecurrently used as a drug of choice in therapy of colorectal cancer. Though effective, newlineits clinical efficacy is limited due to its adverse effects in the form of neurotoxicity, newlinecardiotoxicity, gastrointestinal and hypersensitivity reactions etc. newlineObjective: The objective of the present research work was to prepare and evaluate a newlinebiodegradable, thermo and pH dual responsive oxaliplatin-loaded chitosan-graft-poly- newline(N-isopropylacrylamide) (CS-g-PNIPAAm) co-polymeric nanoparticles as a tumor- newlinetargeting drug delivery system. newlineMethodology: CS-g-PNIPAAm co-polymers were synthesized by surfactant free newlinedispersion co-polymerization method, characterized and optimized its thermo and pH newlineresponsive properties for tumor pH and temperature conditions by changing the newlineconcentrations of chitosan and N,N-methylenebisacrylamide (MBA). To achieve high newlinedrug loading, different drug loading approaches like direct drug loading during newlinepolymerization and self-assembly methods were used and evaluated for percent drug newlineloading efficiency (% LE) and percent drug content (% DC). Optimized co-polymer newlinecould be efficiently loaded with oxaliplatin by self-assembly method in nanoparticle newlineform and evaluated for their morphology (TEM), drug content, particle size, particle newlinecharge and loading efficiency. In vitro release profile of loaded drug was obtained at newlinedifferent pH values (5.5, 6.0, 6.5 and 6.8) at 40 newlineXVIII newline newline0 newlineC temperature and at physiological newlinepH and temperature conditions. In vitro cytotoxicity study was performed on human newlinecolon carcinoma cell lines (HT-29) and human fibroblast cell lines (NIH). Cell uptake newlineof nanoparticles was studies by fluorescence microscopy. newlineResults: Dual responsive (temperature and pH) co-polymers CS-g-PNIPAAm were newlinesuccessfully synthesized and optimized. High oxaliplatin loading was achieved by newlineself-assembly method. Particle size of OXA- loaded nanoparticles was 162±11 nm newlinewith zeta potential of about 54 ±12 mV. The perce