环孢素A纳米粒-凝胶制剂的制备及兔泪液药动学

A novel solid lipid nanoparticles loaded in situ gel for CyA delivery and its lacrimal pharmacokinetics in rabbit tears

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 solid lipid nanoparcles（SLNs） in situ gel for cyclosporine A（CyA） and investigate its lacrimal pharmacokinetics. Methods CyA-loaded SLNs were prepared by emulsion-ultrasonication method and coated with stearylamine as charge modifier. The particle size and potential were determined by Coulter LS230 and Nicom-380 separately. The SLNs loaded in situ gel （ SLN-Gel ） was prepared by adding F127 into the SLNs suspension. The concentration of CyA in rabbit＇s tears was determined by HPLC at different times after ocular administration of 50 μL SLNs, coated SLNs, SLN-Gel, CyA loaded caster oil was chosen as control. The pharmacokinetic parameters were calculated by computer according to one-compartment model. Results The mean particle size of CyA-loaded SLNs was 121 nm, Zeta potential was ＋23 my. The mean residence time（MRT）value and the area under concentration（AUC） of CyA in SLN- Gel formulation were 3.4 and 4 times higher than those of CyA in caster oil. MRT and AUC of CyA in coated SLNs were also found to be significantly higher compared with those of CyA uncoated SLNs. Conclusions SLN-Gel for CyA can greatly increase the concentration of CyA in rabbit tears, enhance the pre-ocular retention time with less irritation.