Guanosine Monophosphate Induced Solubilization of Folic Acid Leading to Hydrogel Formation for Targeted Delivery of Hydrophilic and Hydrophobic Drugs

Hydrogels are emerging as one of the most sought-after drug carriers due to their biocompatibility, high water content mimicking tissue-like environment, injectability, and stimuli responsiveness. Sustained drug release accompanied by targeted delivery to cancer cells can abate numerous adverse side effects of conventional chemotherapy. Folate receptors are overexpressed in various cancer cells, and their high binding affinity to folic acid (FA) makes folic acid-anchored drug carriers a specific targeting entity. Reports of folic acid-based hydrogels are still scarce, owing to their low solubility in water. In this study, we present a simple approach to generate a self-assembled supramolecular hydrogel by employing an amphiphilic low molecular weight gelator (LMWG), guanosine monophosphate (GMP), which noncovalently interacts and coassembles with FA. The hydrogel shows biocompatibility, thermoreversibility, self-healing, injectability, thixotropy, and self-adhesive properties. The hydrogel could encapsulate and release both hydrophilic (doxorubicin) and hydrophobic (curcumin) drugs in a sustained manner. <i>In vitro</i> studies on cancer cells showed that encapsulating the drugs within the hydrogel matrix resulted in enhanced uptake by the cancer cells, thereby increasing their therapeutic efficacy through upregulating tumor suppressor, apoptotic gene expression, and inhibiting cell proliferation markers. Thus, a straightforward fabrication procedure, cost-effectiveness, and treatment potency make the FA-GMP hydrogel a promising drug carrier for practical use in biomedical applications.