Development of cytarabine-loaded pH-responsive polymeric hydrogel: an in vitro and in vivo evaluation.

This study aimed to develop a pH-responsive polymeric hydrogel for the controlled delivery of cytarabine for the treatment of acute leukemia. The polymeric hydrogel was synthesized via free radical polymerization using pluronic acid F127, PEG-800, and agarose as a polymer, and crosslinked via methylene bis acrylamide. The optimized formulation (PPA12) was investigated for cytarabine loading (%), thermal analysis, compatibility of formulation ingredients, swelling trend, morphology, release kinetics, and toxicity in rabbits. Cytarabine loading increased with increase in ratio of polymer, monomer, and pH. The developed hydrogels exhibited excellent swelling behavior at pH 7.4. Cytarabine release occurred in a controlled fashion over a time period of 24 h. Based on the regression coefficient (R2), the best-fit model was of the zero order. Structural entanglement was confirmed by Fourier-transform infrared spectroscopy (FTIR) studies, which confirmed the formation of a hydrogel blend. Toxicity studies have revealed no signs of ocular, oral, or dermal toxicity, thereby ensuring safety and biocompatibility. Therefore, these findings strongly suggest that the developed and optimized polymeric hydrogel (PPA12) is biocompatible, capable of delivering cytarabine at a particular pH, and can be a carrier of choice for targeted drug delivery.