Preparation and evaluation of folic acid modified succinylated gelatin micelles for targeted delivery of doxorubicin

Abstract In this study, novel folic acid modified succinylated gelatin (FA-SG) micelles were prepared and used as drug carrier in folate-receptor (FR) targeted antitumor therapy. FA-SG copolymer was synthesized and characterized by 1 H NMR and fluorescence spectroscopy. Doxorubicin-loaded FA-SG (DOX-FA-SG) micelles were prepared by a dialysis method. The shape of DOX-FA-SG micelles was almost spherical by transmission electron microscopy analysis. The mean diameter of DOX-FA-SG micelles was 277 nm, and the DOX-loading content was 12.4%. In vitro drug release of DOX-loaded micelles showed sustained release behavior for 168 h. DOX-FA-SG demonstrated significantly greater cellular uptake and cytotoxicity against FR-positive MCF-7 cells than the non-targeted DOX-loaded micelles. Importantly, DOX-FA-SG micelles exhibited higher antitumor activity in MCF-7 tumor-bearing mice than doxorubicin hydrochloride (DOX⋅HCl) and DOX-loaded micelles without FA modification. Taken together, FA-SG micelles could be an effective carrier for targeted drug delivery.