Poly Lactic Co-glycolic Acid d-α-tocopheryl Polyethylene Glycol 1000 Succinate Fabricated Polyethylene Glycol Hybrid Nanoparticles of Imatinib Mesylate for the Treatment of Glioblastoma Multiforme
Authors: Bhattacharya Sankha , Shinde Prafull , Page Amit , Prajapati Bhupendra G. 
Published: January 2025

Aims:
This study aimed to develop Imatinib Mesylate (IMT)-loaded Poly Lactic-co-Glycolic
Acid (PLGA)-D-α-tocopheryl polyethylene glycol succinate (TPGS)- Polyethylene glycol (PEG) hybrid
nanoparticles (CSLHNPs) with optimized physicochemical properties for targeted delivery to glioblastoma
multiforme.

Background:
Glioblastoma multiforme (GBM) is the most destructive type of brain tumor with several
complications. Currently, most treatments for drug delivery for this disease face challenges due to the
poor blood-brain barrier (BBB) and lack of site-specific delivery. Imatinib Mesylate (IMT) is one of the
most effective drugs for GBM, but its primary issue is low bioavailability. Therefore, nanotechnology
presents a promising solution for targeted IMT delivery to GBM. This article primarily explores the fabrication
of IMT-loaded core-shell lipid-polymer hybrid nanoparticles (CSLHNPs) to achieve enhanced
brain delivery with therapeutic efficacy.

Objective:
The primary objective of this study is to develop optimized, stable IMT-loaded hybrid nanoparticles
with an encapsulated polymer matrix and to evaluate these nanoparticles using sophisticated instruments
such as SEM and TEM to achieve smooth, spherical nanoparticles in a monodispersed phase.

Method:
The enhanced stable formulation yielded a notable increase in entrapment efficiency, reaching
58.89 ± 0.5%. The physical stability analysis of nanoparticles was assessed over 30 days under conditions
of 25 ± 2°C and 60 ± 5% relative humidity. Hemolytic assays affirmed the biocompatibility and
safety profile of the nanoparticles. in vitro drug release kinetics revealed a sustained IMT release over 48
hours.

Results:
The formulated CSLHNPs achieved a narrow size distribution with a mean vesicle diameter of
155.03 ± 2.41 nm and a low polydispersity index (PDI) of 0.23 ± 0.4, indicating monodispersity. A high
negative zeta potential of -23.89 ± 3.47 mV ensured excellent colloidal stability in physiological conditions.
XRD analysis confirmed the successful encapsulation of IMT within the nanoparticle matrix, with
the drug transitioning to an amorphous state for enhanced dissolution. During Cell-Cell viability assays
on LN229, glioblastoma cells were treated with IMT-loaded nanoparticles and showed a significantly enhanced
inhibitory effect compared to free IMT. These hybrid nanoparticles demonstrated potential in reducing
oxidative stress-induced cellular damage by mitigating reactive oxygen species (ROS). Thus, the
prepared IMT hybrid nanoparticles showed higher cellular uptake and superior cytotoxicity compared to
the plain drug.

Conclusion:
This study posits the IMT-PLGA-TPGS-DSPE PEG 2000-CSPLHNPs as a formidable and
innovative drug delivery system for Glioblastoma Multiforme (GBM) treatment, warranting further exploration
into their clinical application potential. Future work could involve conducting in vivo studies to
evaluate the pharmacokinetics, biodistribution, and therapeutic efficacy of the IMT-PLGA-TPGS-DSPE
PEG 2000-CSPLHNPs in animal models of Glioblastoma Multiforme (GBM). Additionally, further research
may focus on optimizing the nanoparticle formulation for enhanced targeting capabilities, investigating
long-term stability under varied storage conditions, exploring potential combination therapies to
synergize with the nanoparticles, and assessing the scalability and manufacturability of the developed
drug delivery system for potential clinical translation. Integration of advanced imaging techniques for real-
time tracking and visualization of nanoparticle distribution within tumours could also be a promising
direction for future investigations.