Nanjing Forestry Univ, Coll Chem Engn, Nanjing 210037, Nanjing, PR China; Nanjing Forestry Univ, Coinnovat Ctr Efficient Proc & Utilizat Forest Re, Nanjing 210037, Jiangsu, PR China.
Nanjing Forestry Univ, Coll Chem Engn, Nanjing 210037, Nanjing, PR China.
Colloids Surf B Biointerfaces. 2020 Jun;190:110925. doi: 10.1016/j.colsurfb.2020.110925. Epub 2020 Mar 2.
In this work, dual drug loaded in chitosan/dextran sulfate/chitosan (CS/DEX/CS) nanoparticles was synthesized by layer-by-layer (LBL) self-assembly technique for use in anti-cancer drug delivery. The nanoparticles were characterized in terms of particle size, zeta-potential, encapsulation efficiency and morphology (SEM and TEM). The in vitro release of the dual drugs, inner PTX and outer 5-Fu, from the CS-PTX/EX/CS-5Fu nanoparticles with different numbers of CS and DEX layers and different PBS was characterized. The results revealed that the pH-sensitive dual drug loaded nanoparticles exhibited a controlled release profile, and the release mechanism followed Two-phase kinetic model for PTX and Higuchi model for 5-Fu. Subsequently the cytotoxicity of nanoparticles was evaluated against HepG2 cells using MTT and apoptosis assay, resulting in synergistic effects between dual drugs and enhanced inhibition to cancer cells. Cellular uptake studies demonstrated efficient internalization of PTX and 5-Fu in HepG2 cells. Therefore the dual drug loaded CS/DEX/CS nanoparticles had good prospects for the biomedical delivery application.
在这项工作中，通过层层自组装技术合成了载有两种药物的壳聚糖/葡聚糖硫酸盐/壳聚糖（CS/DEX/CS）纳米粒子，用于抗癌药物传递。通过粒径、zeta 电位、包封效率和形态（SEM 和 TEM）对纳米粒子进行了表征。研究了不同 CS 和 DEX 层数和不同 PBS 条件下 CS-PTX/EX/CS-5Fu 纳米粒子中外层 5-Fu 和内层 PTX 的双重药物释放情况。结果表明，这种 pH 敏感的双重药物负载纳米粒子呈现出一种控制释放的模式，其释放机制遵循 PTX 的两相动力学模型和 5-Fu 的 Higuchi 模型。随后，通过 MTT 和细胞凋亡实验评估了纳米粒子对 HepG2 细胞的细胞毒性，结果表明双重药物具有协同作用，并增强了对癌细胞的抑制作用。细胞摄取研究表明，PTX 和 5-Fu 能够有效地被 HepG2 细胞内化。因此，载有双重药物的 CS/DEX/CS 纳米粒子在生物医学传递应用方面具有良好的前景。
