INNOVATIVE STRATEGIES IN BRAIN CANCER DRUG DISCOVERY AND TARGETED DELIVERY: ADVANCES AND CHALLENGES IN PRECISION MEDICINE

Abstract

Brain cancer is still among the most difficult malignancies to treat because of the complexity of blood-brain barrier (BBB), heterogeneity of tumors and low effectiveness of currently implemented drugs. In India, glioblastoma multiforme (GBM) is a disease that is increasingly becoming a major cause of CNS tumor and there is an urgent need to formulate the precision medicine-based drug discovery and targeted delivery models. This paper analyses in vitro and preclinical metadatas of a newly developed polymeric nanoparticle-based targeted drug delivery system of temozolomide (TMZ), the current standard-of-care drug of GBM. PLGA was conjugated with transferrin ligands in order to develop nanoparticles that improve BBB penetration and uptake in tumor cells. There was an evaluation of drug loading, release kinetics, cytotoxicity (U87MG cell line) and BBB permeation in an in vitro Transwell model and preclinical pharmacokinetic and tumor regression studies in Wistar rats with induced orthotactic gliomas. The findings showed an improved drug loading, longer release, 2.5 times increased BBB permeability and a much better tumor suppressive activity in comparison with free TMZ. This experimental study is translational in nature and it focuses on India with relevance to the pharmacological use of the ligand-based nanocarriers in the management of brain cancer.