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.

摘要

由于其独特的尺寸和物理特性，功能化超顺磁性氧化铁纳米颗粒在化学疗法中作为药物载体的使用呈指数增长。在这项研究中，我们通过共沉淀和悬浮方法合成了壳聚糖涂层的功能化超顺磁性氧化铁纳米粒子 (CS-SPIONPs)。后来，我们专注于与戊二醛的交联以及与包括表柔比星 (EPI) 和替莫唑胺 (TMZ) 在内的抗癌药物的配方开发。通过各种表征技术，如透射电子显微镜、X 射线衍射、热重分析、X 射线光电子能谱、傅里叶变换红外光谱和 Zeta 电位研究，研究了 CS-SPIONPs 的形态、磁性、结晶和热性能。表征研究表明，EPI 药物通过亚胺 (-C = N-) 键与 CS-SPIONPs 结合，在较低的 pH 值（4.4-6.4）下对裂解敏感，促进药物释放，并证实壳聚糖的涂层与氧化铁纳米粒子的超顺磁性。CS-SPIONPs 合成的优化研究表明，更大量的壳聚糖 (200 mg)、更低浓度的硫酸亚铁 (0.01 M) 和低搅拌速率 (200 rpm) 适合 EPI 和 TMZ 的最大封装。在不同的 pH 值下进行受控药物释放研究，结果表明 EPI 和 TMZ 释放都随着 pH 值的降低而增加。在 pH 4.6 时，EPI 的最大累积药物释放为 94.06%，TMZ 为 84.67%。