The Influence of Ionizing Radiation on Paclitaxel-Loaded Nanoparticles Based on PLGA

Autor: Izabela M. Domańska, Ramona Figat, Aldona Zalewska, Krystyna Cieśla, Sebastian Kowalczyk, Karolina Kędra, Marcin Sobczak
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Applied Sciences, Vol 13, Iss 19, p 11052 (2023)
Druh dokumentu: article
ISSN: 2076-3417
DOI: 10.3390/app131911052
Popis: The effect of ionizing radiation (γ-rays and electron beam) on anticancer drug delivery systems (DDSs) properties was evaluated concerning potential sterilization. For this purpose, paclitaxel (PTX)-loaded nanoparticles were obtained using a biodegradable, self-developed copolymer of l-lactide and glycolide (PLGA), synthesized in the presence of bismuth 2-ethylhexanoate catalyst. The nanoparticles were obtained with a high encapsulation efficiency of PTX (EE = 94.2%). The average size of the nanoparticles was 253.5 nm. The influence of irradiation (sterilization dose, 25 kGy) on the microstructure and the physicochemical and thermal properties of the polymer matrix was investigated, as well as the effect of irradiation on the morphology and physicochemical properties of the pharmaceutical formulations of the nanoparticles. Additionally, an in vitro drug release study was conducted regarding any alterations in the kinetic profiles of drug release. It was confirmed that the irradiation with both types of ionizing radiation, i.e., γ-rays and electron-beam (EB), slightly decreased the average molecular weight of the polymer matrix. While only negligible changes in the microstructure and thermal properties of PLGA were observed after irradiation with EB, the average length of lactidyl blocks (lLL) in the copolymer chains irradiated with γ-rays decreased from 4.33 to 3.35. Moreover, the contribution of crystalline phase (Xc) in γ-irradiated samples decreased significantly from 35.1% to 22.7%, suggesting a dominant mechanism of chain scission over cross-linking in PLGA samples irradiated with γ-rays. In vitro drug release results demonstrate a sustained and controlled release of PTX from the nanoparticles based on PLGA. The kinetics of drug release was defined as first order with non-Fickian diffusion. Only negligible differences in the kinetic profiles of PTX release from PLGA drug carriers were observed after irradiation. The overall results suggest good resistance of PLGA nanoparticles to irradiation within the conditions used and the great potential of EB in the sterilization process of the polymeric DDSs.
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