Fabrication and Evaluation of Hyaluronic Acid-Coated Albumin Nanoparticles for Delivery of Gemcitabine

Background: Gemcitabine (Gem) is a well-known antineoplastic drug used to treat several solid tumors. The clinical application of Gem is hampered owing to its non-selectivity, short half-life, and drug resistance, which, therefore, necessitate the development of a suitable novel formulation that can selectively target cancer sites. Methods: In present work, Gem-loaded bovine serum albumin nanoparticles (Gem-BSANPs) have been prepared by using the desolvation cross-linking method and coated with hyaluronic acid (HA-Gem-BSANPs) to target the CD44 receptor which overexpressed on several solid tumors. The developed NPs were characterized by particle size, zeta potential, Transmission Electron Microscopy (TEM), and Differential Scanning Calorimetry (DSC). Further anticancer activity of the developed formulation was evaluated against A549 and MCF-7 cells and explored mode of action studies. Results: The mean particle size and zeta potential of HA-Gem-BSANPs were observed as 144.7±5.67 nm and -45.72±3.24 mV, respectively. The TEM analysis also corroborated the particle size and shape, while thermal analysis (DSC) indicated that Gem was entrapped into NPs in an amorphous form. The nucleoside transport inhibition assay demonstrated that the NPs do not depend on transporters for cellular internalization, and hence, resistance development in cells is less expected against this formulation. HA-Gem-BSANPs exhibited higher cytotoxicity and apoptosis on both the tested cell lines. However, better cell-killing ability and mitochondrial membrane potential loss were observed against A549 due to CD44 expression. Conclusion: The present work demonstrated that HA-Gem-BSANPs could be a potential strategy to improve Gem's therapeutic efficacy by selectively targeting the tumor site.