Transferrin-modified Gemcitabine Encapsulated Polymeric Nanoparticles Persuaded Apoptosis in U87MG Cells and Improved Drug Availability in Rat Brain: An Active Targeting Strategy for Treatment of Glioma

Abstract

Among primary brain tumors, glioma has one of the highest fatality rates. Routine chemotherapy often faces off-target drug loss and sub-optimal drug availability at brain tissue. The present study aims at the development of transferrin-conjugated gemcitabine loaded poly (lactic co glycolic acid) nanoparticles (Tf-GB-PLGA-NPs) targeted strategy for brain cancer cell. GB-PLGA-NPs were prepared using solvent evaporation and nanoprecipitation method and then conjugated with Tf. The formulation was characterized for physicochemical parameters, in-vitro release, cytotoxicity, apoptosis (U87MG cell line), and in-vivo pharmacokinetic study. Tf-GB-PLGA-NPs showed 143±6.23 nm of particle size, 0.213 of PDI, –25 mV of zeta potential, and 77.53±1.43% of entrapment efficiency, respectively. Tf-GB-PLGA-NPs exhibited spherical morphology and sustained release of GB (76.54±4.08%) over 24 h. Tf-GB-PLGA-NPs exhibited significant (p < 0.05) cell inhibition against cell line (U87MG) than GB-PLGA-NPs and pure GB. The Tf-GB-PLGA-NPs exhibited higher U87MG apoptosis (61.25%) than GB-PLGA-NPs (31.61%). The Tf-GB-PLGA-NPs exhibited a significantly higher concentration in the brain than pure GB and GB-PLGA-NPs. Tf-GB-PLGA-NPs showed 11.16-fold higher AUC0-t (bioavailability) than pure GB solution and 2.23-fold higher bioavailability than GB-PLGA-NPs. The finding concludes that the Tf-GB-PLGA-NPs are an alternative potent carrier for GB to brain delivery for treating brain cancer.

graphical abstract