Synthesis of biopolymer coated functionalized superparamagnetic iron oxide nanoparticles for the pH-sensitive delivery of anti-cancer drugs epirubicin and temozolomide

Abstract

Functionalized superparamagnetic iron oxide nanoparticles uses are increasing exponentially in chemotherapy as drug vehicles due to their unique size and physical properties. In this study, we have synthesized chitosan coated functionalized superparamagnetic iron oxide nanoparticles (CS-SPIONPs) by co-precipitation and suspension methods. Later, we focused on crosslinking with glutaraldehyde and the development of a formulation with anticancer drugs including Epirubicin (EPI) and Temozolomide (TMZ). The morphological, magnetic, crystalline and thermal properties of the CS-SPIONPs were investigated by various characterization techniques such as transmission electron microscopy, X-ray diffraction, thermal gravimetric, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy and Zeta potential studies. Characterization studies revealed that the EPI drug was conjugated with CS–SPIONPs through imine (–C = N–) bond, which is sensitive to cleavage at lower pH (4.4–6.4), facilitates drug release and also confirms the coating of chitosan along with the superparamagnetic nature of Iron oxide nanoparticles. Optimization studies of CS-SPIONPs synthesis indicated that a greater amount of chitosan (200 mg), less concentration of ferrous sulfate (0.01 M) and low stirring rate (200 rpm) were appropriate for maximum encapsulation of EPI and TMZ. Controlled drug release studies were conducted at various pHs the results depicted that both EPI and TMZ release increased with a decreasing pH. The maximum cumulative drug release at pH 4.6 was 94.06% for EPI and 84.67% for TMZ. Drug release data was fitted to various kinetic models and the Higuchi model which exhibited a high degree of correlation coefficient 0.9966 and 0.9899 for EPI and TMZ, respectively.