Development and evaluation of folate functionalized albumin nanoparticles for targeted delivery of gemcitabine

Gemcitabine is one of the most potent anticancer agents acting on a wide range of solid tumors, however, its use is limited by short half life and high dose leading to serious side effects. The present investigation describes the development and characterization of folate functionalized gemcitabine loaded bovine serum albumin nanoparticles (Fa-Gem-BSANPs). The nanoparticles were prepared by desolvation cross-linking technique and characterized for various parameters including morphology, particle size, zeta potential, drug loading and release profile. The particle size of Gem-BSANPs and Fa-Gem-BSANPs was found to be 159.1 +/- 5.29 and 208.7 +/- 1.80 nm, respectively. DSC and XRD analysis indicated amorphous nature of the drug within the particles. The encapsulated gemcitabine exhibited less hemolytic properties as compared to native drug. The anticancer activity of Fa-Gem-BSANPs was evaluated in folate receptor over expressing cell lines (Ovcar-5 and MCF-7) and folate receptor deficient cell line (MIAPaCa2). The Fa-Gem-BSANPs showed superior anticancer activity as compared to Gem-BSANPs in Ovcar-5 and MCF-7 cells while no significant difference in cytotoxicity was found with MIAPaCa-2 cells. Confocal microscopy indicated facilitated intracellular uptake of Fa-Gem-BSANPs in MCF-7, which in turn result in a higher potential for apoptosis. Further, Fa-Gem-BSANPs exhibited improved anti-tumor activity in Ehrlich solid tumor model in mice. In conclusion, our study indicates that folate functionalized nanoparticles confer enhance cellular uptake and cytotoxicity for gemcitabine. (C) 2015 Elsevier B.V. All rights reserved.