Preparation of pH-sensitive chitosan/polyvinylpyrrolidone/α-Fe2O3 nanocomposite for drug delivery application: Emphasis on ameliorating restrictions

Abstract

Chitosan (CS)/polyvinylpyrrolidone (PVP)/hematite (α-Fe₂O₃) nanocomposites loaded with Doxorubicin (drug model) were synthesized via an oil-in-water emulsification method to develop a biocompatible and pH-sensitive drug nanocarrier for the first time. A hydrogel, including CS, PVP, and α-Fe₂O₃, was fabricated successfully with glutaraldehyde (GA) as the cross-linker. Incorporating α-Fe₂O₃ into CS/PVP hydrogel improved the pH-sensitivity and developed beneficial hydrogel. FTIR and XRD analysis illustrated physical interactions between polymer-polymer, polymer-drug, and crystalline behavior of prepared nanocomposite. These analyses also confirmed chemical bonding in nanocomposite's structure. The FE-SEM analysis showed successful impregnation of α-Fe₂O₃ into CS/PVP matrix and spherical structure. To clarify the size distribution and surface charge of the drug-loaded nanocomposite (CS/PVP/α-Fe₂O₃/Dox), DLS and zeta analyses were conducted. They showed the mean size of nanocomposites at about 247 nm. Drug-loaded CS/PVP/α-Fe₂O₃ nanocomposite and CS/PVP/Dox were studied for their release behavior and kinetics. Furthermore, the effect of α-Fe₂O₃ on release from CS/PVP/α-Fe₂O₃/Dox nanocomposite was investigated. That showed an increase in encapsulation of Doxorubicin and beneficial release behavior such as slow-release and retention effect. The release from this drug-loaded nanocomposite revealed excellent pH-sensitive and controlled release of the drug. Besides, the in vitro cytotoxicity and cell apoptosis were studied to recognize biological properties. These analyses revealed that drug-loaded nanocomposite caused high inhibition to MCF-7 cells in presence of α-Fe₂O₃ and proved the hematite's anti-cancer effect. By and large, this study confirmed CS/PVP/α-Fe₂O₃ nanocomposites as a potential candidate for the controlled pH-sensitive release of the drug.

Keywords: Chitosan; Drug delivery; Iron oxide; Polyvinylpyrrolidone; pH-sensitive nanocarrier.