Chitosan nanoparticles as a smart nanocarrier for gefitinib for tackling lung cancer: Design of experiment and in vitro cytotoxicity study

Haitham Amin; Mohammed A Amin; Shaaban K Osman; Ahmed M Mohammed; Gamal Zayed

doi:10.1016/j.ijbiomac.2023.125638

Chitosan nanoparticles as a smart nanocarrier for gefitinib for tackling lung cancer: Design of experiment and in vitro cytotoxicity study

Int J Biol Macromol. 2023 Aug 15:246:125638. doi: 10.1016/j.ijbiomac.2023.125638. Epub 2023 Jun 30.

Authors

Haitham Amin¹, Mohammed A Amin², Shaaban K Osman³, Ahmed M Mohammed⁴, Gamal Zayed⁵

Affiliations

¹ Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt. Electronic address: haithamamin.4522@azhar.edu.eg.
² Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt; Department of Pharmaceutics, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia. Electronic address: m.darwish@qu.edu.sa.
³ Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt. Electronic address: shaabanosman@azhar.edu.eg.
⁴ Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt. Electronic address: ahmedabdelaal@azhar.edu.eg.
⁵ Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt; Al-Azhar Centre of Nanosciences and Applications (ACNA), Al-Azhar University, Assiut 71524, Egypt. Electronic address: gamalzayed@azhar.edu.eg.

PMID: 37392910
DOI: 10.1016/j.ijbiomac.2023.125638

Abstract

Due to its poor solubility and systemic side effects, gefitinib (Gef) has limited application in treatment of lung cancer. In this study, we used design of experiment (DOE) tools to gain the necessary knowledge for the synthesis of high-quality gefitinib loaded chitosan nanoparticles (Gef-CSNPs) capable of delivering and concentrating Gef at A549 cells, thereby increasing therapeutic effectiveness while decreasing adverse effects. The optimized Gef-CSNPs were characterized by SEM, TEM, DSC, XRD, and FTIR analyses. The optimized Gef-CSNPs had a particle size of 158±3.6 nm, an entrapment efficiency of 93±1.2 %, and a release of 97±0.6 % after 8 h. The in vitro cytotoxicity of the optimized Gef-CSNPs was found to be significantly higher than pure Gef (IC₅₀ = 10.08 ± 0.76 μg/mL and IC₅₀ = 21.65 ± 0.32 μg/mL), respectively. In the A549 human cell line, the optimized Gef-CSNPs formula outperformed pure Gef in terms of cellular uptake (3.286 ± 0.12 μg/mL and 1.777 ± 0.1 μg/mL) and apoptotic population (64.82 ± 1.25 % and 29.38 ± 1.11 %), respectively. These findings explain why researchers are so interested in using natural biopolymers to combat lung cancer, and they paint an optimistic picture of their potential as a promising tool in the fight against lung cancer.

Keywords: Apoptosis assay; Cellular drug uptake; Chitosan nanoparticles; Design of experiment; Gefitinib; Lung cancer.