Design and Evaluation of Paclitaxel Loaded Protein Based Nanoparticle For Brain Targeting

Abstract

The effective treatment of brain tumors remains a major challenge due to the restrictive nature of the blood–brain barrier 
(BBB) and the dose limiting systemic toxicity of conventional chemotherapeutics. Paclitaxel, a potent anticancer agent, 
demonstrates limited clinical utility in neuro oncology owing to its poor aqueous solubility, efflux by P glycoprotein pumps, 
and inability to efficiently cross the BBB. To overcome these limitations, the present study focuses on the design, 
development, and evaluation of Paclitaxel loaded protein based nanoparticles for targeted brain delivery. Biocompatible 
and biodegradable proteins were employed as carriers to enhance drug stability, facilitate controlled release, and improve 
brain localization via receptor mediated transcytosis. The nanoparticles were prepared using a nanoprecipitation technique, 
characterized for size distribution, zeta potential, morphology, encapsulation efficiency, and in vitro release kinetics. In 
vitro cytotoxicity assays on glioblastoma cells confirmed enhanced antiproliferative activity of the nanoparticle formulation 
compared to free Paclitaxel. Furthermore, in vivo biodistribution studies in rodent models revealed significantly elevated 
brain accumulation, indicating successful penetration across the BBB. Pharmacokinetic analysis demonstrated prolonged 
circulation time and reduced off target drug exposure. Collectively, these findings suggest that protein based Paclitaxel 
nanoparticles provide a promising platform for safer and more effective brain tumor therapy, paving the way for 
translational applications in neuro oncology.