Khushboo Jani

St John’s University, United States

Title: Formulation of Temozolomide Loaded Magnetic Nanoparticles: In Vitro and In Vivo Evaluation for Glioblastoma Multiforme

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Biography

Khushboo worked on targeting brain tumor by formulating and characterizing magnetic nanoparticles loaded with the chemotherapeutic agent. She also performed Pharmacokinetic analysis and biodistribution studies to ensure the brain targeting efficacy of the formulation. Prior to her PhD, she worked in DMPK department at Glenmark Pharmaceuticals, where she developed a model for In vitro and in vivo screening of acetaminophen induced hepatotoxicity and modulation by co-administered drugs. She is recipient of ‘Best Abstract’ award, AAPS PharmSci 360 2020. Her team was awarded the ‘Best Student Chapter’ in AAPS PharmSci 360, Nov 2019). She has led and hosted regional conference GRASP in 2018 at St John’s University. 

Abstract

Glioblastoma multiforme (GBM) is the most common and malignant form of astrocytoma. Although, temozolomide (TMZ) is considered as a standard chemotherapy agent, at least 50% of treated patients do not respond to TMZ due to multidrug resistant phenotype exhibited by GBM cells. This can be overcome by using nano particulate delivery in presence of external physical field to enhance permeation. Thus, a polymeric nanocarrier system encapsulated with TMZ, targeted by the magnetic field, offers a potential alternative to the GBM treatment. The purpose of this study was to synthesize OAMNP as the magnetic core. And then, load in poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid)-methoxy poly(ethylene oxide) (PLA?PEG) nanoparticles (NPS) by single emulsion solvent evaporation technique. The synthesized OAMNP core was characterized for magnetic activity and particle size (i.e., 9 ± 0.3 nm). Transmission electron microscopy analysis exhibited a spherical morphology of the particle. The in vitro characterization for OAMNP TMZ NPS included morphology, particle size, zeta potential, encapsulation efficiency and physical stability. Further, for OAMNP TMZ NPS, drug loading was optimized such that the particle size (i.e., 206.7 ± 1.5 nm) and an encapsulation efficiency of 43% was obtained. The polydispersity index of 0.188 ± 0.002 represented monodispersed system with particles being positively charged (+1.04 ± 0.05 mV). Cytotoxicity assay revealed the IC50 values for TMZ loaded nanoparticles were significantly lower (p<0.05) as compared to the TMZ solution. Transport studies revealed a 10-fold reduction in P-gp mediated efflux of TMZ (based on efflux ratio) observed for OAMNP TMZ NPS in comparison to TMZ in solution. In in vivo study, at the magnetic field strength of 1.6 T, the TMZ exposure in rats increased by 4.6-fold when compared with lower magnetic field exposure and 3.6-fold increase in TMZ distribution was found when compared to the group not exposed to magnetic field.