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

摘要

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 hydro-gel by the hydrolysis of glucono-δ-lactone in PBS buffer under physiological conditions has been reported. The gel has a fi-brillar network morphology attributable to intermolecular H-bonding and p-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 Fick-ian 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 metylthiazolyldiphe-nyltetrazolium 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.