PEG Functionalized Stimuli Responsive Self-Healable Injectable Dynamic Imino-boronate G-quadruplex Hydrogel for the Delivery of Doxorubicin.

Abstract

Dynamic G-quadruplex hydrogel is engineered by using guanosine, 2-formylphenylboronic acid, and 4-Arm PEG-NH2. The gelation conditions are optimized by varying concentrations of the gelators, pH, and different alkali metal ions. The formation of imino-boronate bonds during the gelation process is fully characterized with FT-IR, 1H NMR, and 11B NMR spectroscopy. The secondary supramolecular G-quadruplex structure and the formation of nanofibrillar morphology are well examined using several spectroscopic and microscopic techniques. The mechanical strength of the hydrogel is investigated by rheological experiments. The hydrogel is injectable and self-healable due to the dynamic nature of the imono-boronate bonds. The dynamic bonds provide distinct shear-thinning and thixotropic properties to the resulting hydrogel with almost 90% recovery of its mechanical strength after four cycles. The pH responsive behavior of the hydrogel is achieved by pH sensitive imino-boronate bonds, which are unstable at acidic pH. To investigate the biocompatibility of the hydrogel, a wide range of hydrogel concentrations are examined by in vitro cell culture experiments using the MCF-7 cell line. After a biocompatibility test of the hydrogel, the anticancer drug doxorubicin is incorporated inside the gel to analyze the drug release profile at different pHs. The release rate of the loaded drug is observed faster in lower pH (pH 4.8) than in physiological pH (pH 7.4). Different release rate of the drug from the drug loaded hydrogel in different pHs is driven by the pH sensitive imino-boronate bonds. The release profile of the drug is slow, sustain and steady.