Development of core-shell nanocarrier system for augmenting piperine cytotoxic activity against human brain cancer cell line

Abstract

Brain tumor has a low prognosis with only 15% survival rate (5 years after diagnosis). Many of the current therapeutics have limited activity due to their inability to cross the blood brain barrier which retards drug accumulation in tumor site and causes drug resistance. Piperine, a phytochemical drug with poor solubility, could be an alternative to current therapeutics after evading its solubility and permeability limitations. Piperine micellization was optimized to improve drug solubility. Positively charged trimethyl-chitosan was synthesized then electrostatically adsorbed onto piperine nanomicelles forming core-shell nanoparticles. Physicochemical and morphological characterizations, and in-vitro release were performed. Cytotoxicity on human brain cancer cell line (Hs683) was evaluated using IC50 determination, cell cycle arrest analysis, apoptosis and enzyme-linked immunosorbent assay. Optimum piperine-loaded core-shell nanoparticles were successfully fabricated with double-phase release model. Significant improvement in cytotoxicity than free drug was noted with increasing in G2/M-phase and pre-GI-phase population, apoptotic/necrotic rates and inhibition of CDK2a.