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目的制备环孢素A固体脂质纳米粒-原位凝胶复合制剂并考察其在家兔泪液中消除情况。方法采用乳化-超声法制备环孢素固体脂质纳米粒,用带正电的十八胺包衣以调节纳米粒表面的电性,用Cou lter LS 230测定纳米粒粒径,用电泳光散射法测定纳米粒的动电电位,将包衣纳米粒载于F127形成的原位凝胶中,考察制剂在家兔泪液中不同时间点药物浓度,以环孢素橄榄油滴眼液作对照,计算药物动力学参数。结果纳米粒粒径121 nm,动电电位+23 mv,纳米粒-凝胶制剂在家兔眼部经3 h的泪液代谢动力学参数AUC、MRT分别为蓖麻油制剂的3.4和4.0倍,包衣纳米粒的AUC和MRT也均比未包衣纳米粒有显著提高。结论环孢素A固体脂质纳米粒-原位凝胶制剂可显著提高环孢素在泪液中的浓度,延长作用时间,减少刺激性。
Objective To prepare cyclosporin A solid lipid nanoparticles - in situ gel preparation and investigate its elimination in rabbit tear fluid. Methods Cyclosporine solid lipid nanoparticles were prepared by emulsification-ultrasonication. The surface of the nanoparticles was coated with positively charged octadecylamine. The particle size of the nanoparticles was measured by Coulter LS 230. Electrophoretic light scattering Method was used to determine the electrokinetic potential of the nanoparticles. The coated nanoparticles were loaded on the in-situ gels formed by F127. The drug concentrations of the preparations in rabbits’ tear fluid at different time points were investigated. The cyclosporin olive oil eye drops were used as controls, Pharmacokinetic parameters were calculated. Results The kinetic parameters AUC and MRT of NPs in the rabbit eye after 3 h were 3.4 and 4.0 times higher than that of the castor oil respectively at the particle size of 121 nm and the electrokinetic potential of +23 mv. The AUC and MRT of the coated nanoparticles were also significantly higher than those of the uncoated nanoparticles. Conclusion Cyclosporin A solid lipid nanoparticles - in situ gel preparation can significantly increase the concentration of cyclosporine in the tear, prolong the duration of action and reduce irritation.