Thermo/-pH responsive nanohydrogels for controlled release of doxorubicin

Abstract

Natural polymer-based nanohydrogels have attracted extensive attention due to their unique biocompatibility and biodegradability. The modification of such polymeric structure with thermo- and pH-sensitive moieties would result in the production of intelligent drug delivery system (DDS). Objective In the current study, thermo and pH-responsive nanohydrogels (NHGs) based on chitosan as natural biomaterial was designed and developed. Method For this purpose, N-isopropylacrylamide (NIPAAm) and itaconic acid (IA) were grafted onto CS using free radical copolymerization method in the presence of cross linker agent, subsequently the NHGs were prepared by sonication method. The prepared NHGs were characterized by FT-IR, DLS, and UV-Vis spectroscopy methods. The thermoresponsive behavior of the prepared NHGs was confirmed by the lower critical solution temperature (LCST) measurement. Doxorubicin (DOX) was loaded into NHGs and its in vitro release was evaluated at different temperatures and pH values. The biological impacts of the prepared NHGs wereinvestigated via MTT assay in MCF-7 cells. Results The prepared NHGs indicated the size distribution around 200 nm and LCST around of 39 ˚C. The NHGs showed the drug loading efficiency around 80% and release study confirmed sustained release behavior that was accelerated at lower pH values. The MTT results didn’t show statically significant differences between free DOX and drug-loaded NHGs. Based on flowcytometery datas, uptake of drug-loaded NHGs is based on nanohydrogels size. Also, drug-loaded NHGs could lead to the occurrence of cell apoptosis with the same extent as free DOX. Discussion Based on these findings, the developed NHGs could be considered as a promising smart DDS for the efficient therapy of cancer, however the targeting potential of such delivery system should be addressed by in vivo experiments, in which the impact of passive targeting by enhanced permeability and retention phenomena could be addressed appropriately.