Zhu Xuan, Su Meiqin, Tang Shaoheng, Wang Lingsong, Liang Xinfang, Meng Feihong, Hong Ying, Xu Zhiran
School of Pharmaceutical Science, Xiamen University, Xiamen, China.
Mol Vis. 2012;18:1973-82. Epub 2012 Jul 18.
The goal of the present study was to synthesize mucoadhesive polymer - thiolated chitosan (TCS) from chitosan (CS), then prepared CS/TCS-sodium alginate nanoparticles (CS/TCS-SA NPs), determined which was more potential for ocular drug delivery.
A new method for preparing TCS was developed, and the characteristics were determined using Fourier transform infrared spectroscopy and the degree of thiol immobilized was measured by Ellman's reagent. Human corneal epithelium (HCE) cells were incubated with different concentrations of TCS for 48 h to determine the cell viabilities. CS/TCS-SA NPs were prepared and optimized by a modified ionic gelation method. The particle sizes, zeta potentials, Scanning electron microscopy images, mucoadhesion, in vitro cell uptake and in vivo studies of the two types of NP were compared.
The new method enabled a high degree of thiol substitution of TCS, up to 1,411.01±4.02 μmol/g. In vitro cytocompatibility results suggest that TCS is nontoxic. Compared to CS-SA NPs, TCS-SA NPs were more stable, with higher mucoadhesive properties and could deliver greater amounts of drugs into HCE cells in vitro and cornea in vivo.
TCS-SA NPs have better delivery capability, suggesting they have good potential for ocular drug delivery applications.
本研究的目的是从壳聚糖（CS）合成粘膜粘附聚合物 - 硫醇化壳聚糖（TCS），然后制备CS/TCS - 海藻酸钠纳米颗粒（CS/TCS - SA NPs），确定哪种更具眼部给药潜力。
开发了一种制备TCS的新方法，使用傅里叶变换红外光谱法测定其特性，并用Ellman试剂测量硫醇固定化程度。将人角膜上皮（HCE）细胞与不同浓度的TCS孵育48小时以确定细胞活力。通过改良的离子凝胶法制备并优化CS/TCS - SA NPs。比较了两种类型纳米颗粒的粒径、zeta电位、扫描电子显微镜图像、粘膜粘附性、体外细胞摄取和体内研究。
新方法使TCS的硫醇取代度很高，达到1,411.01±4.02μmol/g。体外细胞相容性结果表明TCS无毒。与CS - SA NPs相比，TCS - SA NPs更稳定，具有更高的粘膜粘附性能，并且在体外可以将更多药物递送至HCE细胞，在体内可递送至角膜。
TCS - SA NPs具有更好的递送能力，表明它们在眼部给药应用中具有良好的潜力。
