Injectable, Self-Healing, and Stress Sustainable Hydrogel of BSA as a Functional Biocompatible Material for Controlled Drug Delivery in Cancer Cells

Hydrogels have been used in the literature in tissue engineering, in drug delivery, and as enzyme biomimics. Herein, we report the synthesis of a functional biomaterial using BSA as scaffold and epichlorohydrin as cross-linker. The hydrogels reported in this paper were shown to exhibit tunable pore size as a function of BSA concentration by scanning electron microscopy (SEM) and, therefore, are well suited to encapsulate drug molecules for delivery applications. These are injectable, shear thinning, self-healing, and has the ability to withstand a physical weight of similar to 300 times of its own. In trypsin medium, the gel is degraded by 50% in 36 h supporting that these are biodegradable. The loading of Dox by the gel was confirmed by the emission of red fluorescence and also by filling the pores by fibrillar structures as demonstrated by SEM. The controlled release of Dox occurs over 5 days to an extent of 37 +/- 2%, 26 +/- 0.5%, and 21 +/- 1.5% in PBS at pH 5.5, 6.8, and 7.4 respectively. Since these hydrogels are made of BSA as matrix, their biocompatibility was proven by MCF-7, HeLa, and MDA-MB-231 cells wherein 95 +/- 5% of cells are viable when treated with unloaded hydrogel. However, the Dox loaded hydrogel results in 70-80% of killing in the case of all three cancer cells. Fluorescence microscopy and FACS studies support controlled and time dependent release of Dox in MCF-7 cells for 24 h where the drug goes into cytoplasm initially and then into nucleus. The cell cycle analysis carried out using MCF-7 cells clearly showed that the cell death is due to apoptosis, and this is by arresting the G(2)/M phase as a function of time. All of the data supports the utility of the synthesized BSA hydrogel as a biomaterial that will find application in controlled drug delivery