Injectable Hydrogel of Vitamin B9 for the Controlled Release of Both Hydrophilic and Hydrophobic Anticancer Drugs

Abstract

Folic acid (FA), vitamin B9, is a good receptor of drugs triggering cellular uptake via endocytosis. FA is sparingly soluble in water. Herein, a new approach for the formation of FA hydrogel by the hydrolysis of glucono-δ-lactone in PBS buffer under physiological conditions has been reported. The gel has a fibrillar network morphology attributable to intermolecular H-bonding and π-stacking interactions. The thixotropic property of the gel is used for the encapsulation of both hydrophilic [doxorubicin (DOX)] and hydrophobic [camptothecin (CPT)] drugs. The loading of DOX and CPT into the gel is attributed to the H-bonding interaction between FA and drugs. The release of DOX is sustainable at pH 4 and 7, and the Peppas model indicates that at pH 7 the diffusion of the drug is Fickian but it is non-Fickian at pH 4. The release of CPT is monitored by fluorescence spectroscopy, which also corroborates the combined release of both drugs. The metylthiazolyldiphenyltetrazolium bromide assay of FA hydrogel demonstrates nontoxic behavior and that the cytotoxicity of the DOX-loaded FA hydrogel is higher than that of pure DOX, with a minimal effect on normal cells.