Development and Optimization of Irinotecan-Loaded PCL Nanoparticles and Their Cytotoxicity against Primary High-Grade Glioma Cells

Basant Salah Mahmoud, Christopher McConville

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Abstract

BACKGROUND: High-grade gliomas (HGGs) are highly malignant tumors with a poor survival rate. The inability of free drugs to cross the blood-brain barrier and their off-target accumulation result in dose-limiting side effects. This study aimed at enhancing the encapsulation efficiency (EE) of irinotecan hydrochloride trihydrate (IRH) within polycaprolactone (PCL) nanoparticles with optimized size and charge.

MATERIALS AND METHODS: IRH-loaded PCL nanoparticles were formulated using either the single emulsion (O/W, W/O and O/O) or double emulsion (W/O/O and W/O/W) solvent evaporation techniques. The nanoparticles were characterized for their size, zeta potential and EE, with the optimized nanoparticles being characterized for their drug release and cytotoxicity.

RESULTS: The amorphization of PCL and the addition of electrolytes to the aqueous phases of the W/O/W emulsion produced spherical nanoparticles with a mean diameter of 202.1 ± 2.0 nm and an EE of 65.0%. The IRH-loaded nanoparticles exhibited zero-order release and were cytotoxic against primary HGG cells.

CONCLUSION: The amorphization of PCL improves its EE of hydrophilic drugs, while the addition of electrolytes to the aqueous phases of the W/O/W emulsion enhances their EE further. IRH-loaded PCL nanoparticles have the potential to deliver cytotoxic levels of IRH over a sustained period of time, enhancing the cell death of HGGs.

Original languageEnglish
Article number541
JournalPharmaceutics
Volume13
Issue number4
DOIs
Publication statusPublished - 13 Apr 2021

Keywords

  • nanoparticles
  • high-grade gliomas
  • polycaprolactone
  • irinotecan
  • emulsification
  • solvent evaporation
  • amorphization
  • electrolytes

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