Fabrication and in vitro evaluation of pH and temperature-dual-responsive β-cyclodextrin inclusion-based supramolecular hydrogel for controlled delivery of doxorubicin

Abstract

This research focused on the fabrication and drug-loading study of a β-cyclodextrin inclusion-based novel supramolecular hydrogel, followed by pH and/or temperature-responsive in vitro drug release study. The supramolecular hydrogel was constructed using two building blocks, specifically, BB1, poly(β-cyclodextrin-co-citric acid) and BB2, citric acid ester of phenyl-mono-capped polyethylene glycol-4000, and characterized. The pH and temperature responsiveness of the resulting BB1:BB2 (w/w), 1:2 hydrogels were investigated using high-performance liquid chromatography (HPLC) under four different conditions, pH 7.4 at 25 °C, pH 4 at 25 °C, pH 7.4 at 37 °C, and pH 4 at 37 °C. Doxorubicin (DOX) loading study of the hydrogel and the in vitro DOX release study from the DOX-loaded hydrogel were investigated under the above-mentioned four different conditions using UV-visible spectroscopy. After applying a stimulus/stimuli, HPLC chromatograms exhibited peak splitting, shift of retention times, and appearance of new peaks. These observations confirmed the disassembly and/or breakdown of the supramolecular network under the influence of stimuli. The BB1:BB2 (w/w), 1:2 hydrogel exhibited the highest drug loading efficiency of 56.7% and drug loading capacity of 0.05% was used for the in vitro DOX release studies. The highest DOX release efficiency of 47% was observed under dual-stimuli conditions, pH 4 and 37 °C, which confirms the pH and temperature dual responsiveness on disassembling and/or breaking down the supramolecular hydrogel. In conclusion, β-cyclodextrin inclusion-based novel supramolecular hydrogel exhibits pH and temperature dual-responsiveness for in vitro DOX delivery which exhibits the potential of the developed supramolecular hydrogel in controlled DOX delivery applications.