吡诺克辛钠-层状双氢氧化物纳米片及插层纳米粒复合物滴眼液的研究

为考察新型药物载体层状双氢氧化物(LDH)纳米片在眼部给药系统的应用,采用LDH纳米片为载体,羧甲基纤维素钠(CMC)为稳定剂,吡诺克辛钠(PRN)为模型药物,制备CMC-PRN-LDH纳米片复合物;采用共沉淀法制备PRN-LDHs插层纳米粒复合物。通过X射线衍射、原子力显微镜、透射电镜、激光粒度仪等对LDH纳米片、CMC-LDH纳米片复合物及两种载药-LDH纳米复合物理化性质进行研究。通过体外稳定性、体外释放、家兔泪液滞留实验比较了两种载药-LDH纳米复合物的差异。结果显示,CMC-PRN-LDH纳米片复合物相对稳定,而PRN-LDHs插层纳米粒稳定性较差,二者12 h体外累积释放百分率分别为70.44%和44.21%。CMC-PRN-LDH纳米片复合物滴眼液的AUC0-6 h和MRT分别为市售滴眼液的4.18和1.79倍,而PRN-LDHs插层纳米粒复合物滴眼液眼部滞留结果差异较大。CMC-PRN-LDH纳米片复合物滴眼液对眼部无刺激性。上述结果表明,LDH纳米片可作为眼部给药载体,能显著提高药物在角膜前的滞留时间。

Ophthalmic solution of pirenoxine sodium-layered double hydroxide nanosheets and intercalated nanoparticles

The aim of this study was to evaluate the potential application of layered double hydroxide(LDH)nanosheets for ocular drug delivery. Using LDH nanosheets as carriers, carboxymethyl cellulose(CMC)as a stabilizer and pirenoxine sodium(PRN)as the model drug, CMC-PRN-LDH nanosheets were prepared. PRN-LDHs nanoparticles were synthesized via co-precipitation method. X-ray diffraction, atomic force microscopy, transmission electron microscopy and laser particle sizer were employed to characterize the physicochemical properties of LDH nanosheets, CMC-LDH nanosheets and PRN-LDH nanocomposites. Stability, accumulative release in vitro and precorneal retention in vivo of both CMC-PRN-LDH nanosheets and PRN-LDHs nanoparticles were evaluated. It was found that CMC-PRN-LDH nanosheets were electrostatically stabilized by CMC absorbed on the surface of LDH nanosheets, but PRN-LDHs nanoparticles aggregated in phosphate buffered saline. 12-hr accumulative release percentage of PRN from CMC-PRN-LDH nanosheets and PRN-LDHs nanoparticles were 70. 44% and 44. 21% in vitro, respectively. Compared with the commercial PRN eye drops, there existed 4. 18-fold increase in AUC_{0-6 h} and 1. 79-fold in mean retention time of CMC-PRN-LDH nanosheets. Negligible levels of PRN-LDHs nanoparticles might be attributed to inter-groups difference. Draize test showed that CMC-PRN-LDH nanosheets were non-irritant to the rabbit eyes after single and repeated dosing. It suggest that this novel LDH nanosheet could be a promising carrier for ocular drug delivery with prolonged residence time.