Development Characterization Optimization Of Surface Engineered Gemcitabne Loaded Plga Nanoparticles Targeting To Brain Tumor

Abstract

ABSTRACT newlineObjectives: The present study aims to develop a transferrin (Tf)-conjugated Gemcitabine (GB) loaded poly (lactic co glycolic acid) nanoparticles (Tf-GB-PLGA-NPs) as an active targeting strategy for brain cancer. Experimental GB-PLGA-NPs were prepared by solvent evaporation and nanoprecipitation method, characterized followed by conjugation with Tf. The formulation was characterized for various physicochemical parameters and assessed for anticancer effectiveness in vitro employing human glioblastoma cells (U87MG cell line). Methods: The formulation process involved two steps. Initially, emulsification was carried out by combining the polymer solution (organic phase) with the surfactant solution (aqueous phase). Subsequently, in the second step, the organic solvent was evaporated, resulting in the precipitation of the polymer and the formation of nanoparticles. The quantity of PLGA, Tween 80, and PVA (at a constant concentration) was adjusted based on the experimental trial approach. Subsequently, GB-PLGA-NPsunderwent characterization, wherein their particle size, encapsulation efficiency, polydispersity index (PDI), and cumulative release were evaluated. Further, the optimized GB-PLGA-NPs/Tf-GB-PLGA-NPswere evaluated for their anticancer effectiveness on U87 MG cells by MTT and apoptosis assay. newlineResults: The optimal formulation composition was determined as 200 mg of PLGA, 4ml of Tween 80, and 2mg of PVA. Tf-GB-PLGA-NPs showed 143±6.23nm 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 24h. Further, significant (Plt0.05) cell inhibition was observed by experimental Tf-GB-PLGA-NPsagainst U87MG than GB-PLGA-NPs and pure GB. Similarly, a higher apoptosis (61.25%) was observed for Tf-GB-PLGA-NPsthan GB-PLGA-NPs (31.61%). Pharmacokinetic data revealed a significantly higher concentration of Tf-GB-PLGA-NPsin the brain than pure GB and GB-PLGA-NPs. An 11.16-fold