Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi 221 005, UP, India.
Eur J Pharm Sci. 2012 Nov 20;47(4):678-85. doi: 10.1016/j.ejps.2012.08.008. Epub 2012 Aug 16.
The objective of the study was to develop chitosan (CH) coated sodium alginate-chitosan (SA-CH) nanoparticles, i.e. CH-SA-CH NPs loaded with 5-FU for ophthalmic delivery. Drug loaded nanoparticles (DNPs) were prepared by ionic gelation technique using sodium alginate (SA) and chitosan (CH) and then suspended in chitosan solution. The mean size of nanoparticles and morphology were characterized by dynamic light scattering, scanning electron microscopy, atomic force microscopy and zeta potential. The in vitro release was studied by dialysis membrane technique. The size and drug encapsulation efficiency were dependent on molar ratio of SA and CH. The size of SA-CH nanoparticles was significantly increased with changed morphology after CH coating. SA-CH nanoparticles did not show any interaction with mucin while an enhanced viscosity was observed on coating of nanoparticles with CH. CH-SA-CH DNPs presented a sustained release of 5-FU compared to the 5-FU solution with high burst effect. In vivo study in rabbit eye showed significantly greater level of 5-FU in aqueous humor compared to 5-FU solution. The enhanced mucoadhesiveness of CH-SA-CH DNPs results in higher bioavailability as compared to the uncoated nanoparticles. Optimized formulation was found non-irritant and tolerable when tested by modified Draize test in rabbit eye.
本研究旨在制备载有 5-FU 的壳聚糖（CH）包覆海藻酸钠-壳聚糖（SA-CH）纳米粒，即用于眼部给药的 CH-SA-CH NPs。采用离子凝胶技术，用海藻酸钠（SA）和壳聚糖（CH）制备载药纳米粒（DNPs），然后悬浮在壳聚糖溶液中。采用动态光散射、扫描电子显微镜、原子力显微镜和zeta 电位对纳米粒的粒径和形态进行了表征。通过透析膜技术研究了体外释放情况。纳米粒的粒径和药物包封效率取决于 SA 和 CH 的摩尔比。CH 包覆后，SA-CH 纳米粒的粒径显著增大，形态发生变化。SA-CH 纳米粒与粘蛋白无相互作用，而纳米粒表面包覆 CH 后，溶液黏度明显增加。与具有高突释效应的 5-FU 溶液相比，CH-SA-CH DNPs 呈现出 5-FU 的持续释放。兔眼体内研究表明，与 5-FU 溶液相比，房水中 5-FU 的水平显著升高。与未包覆的纳米粒相比，CH-SA-CH DNPs 的增强粘膜粘附性导致更高的生物利用度。改良的兔眼Draize 试验表明，优化的配方无刺激性，可耐受。
