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目的制备具有生物黏附性的环孢素纳米脂质载体(NLC)眼用制剂并考察其在家兔泪液中的消除情况。方法采用熔融-乳化法制备NLC,用生物黏附性材料普流罗尼F127(F127)调节制剂黏度,用Zetasizer纳米粒度仪测定纳米粒粒径,HPLC法考察制剂在家兔泪液中不同时间点药物浓度,以未加入F127的NLC作对照,采用Kinetica4.4计算药动学参数。结果 NLC粒径(35.9±0.2)nm,F127-NLC粒径(41.2±0.2)nm。NLC中F127的含量影响制剂的稳定性,高浓度的F127(9.0%)降低NLC的稳定性,而低浓度的F127(≤6.0%)增加NLC的稳定性。含F127 1.7%、3.3%和6.0%的F127-NLC在兔眼部经6h的泪液消除动力学参数AUC分别为NLC的1.57、1.79和2.42倍,MRT分别为NLC的1.19、1.31和1.90倍。结论加入6.0%的F127制备的NLC可显著提高药物在泪液中的浓度,延长作用时间,减少刺激性。
OBJECTIVE To prepare bioadhesive cyclosporin nanocapsules (NLC) ophthalmic preparations and study its elimination in rabbit tear fluid. Methods Melting-emulsifying method was used to prepare NLC. The viscosity of the preparation was controlled by the bioadhesive material Vernil F127 (F127). The particle size of the nanoparticles was determined by Zetasizer nano-particle size analyzer. The drug was determined by HPLC at different time points Concentration, without adding F127 NLC as a control, using Kinetica4.4 pharmacokinetic parameters. Results NLC particle size (35.9 ± 0.2) nm, F127-NLC particle size (41.2 ± 0.2) nm. The content of F127 in NLC affected the stability of the formulation. High concentrations of F127 (9.0%) decreased the stability of NLC, while low concentrations of F127 (≤6.0%) increased the stability of NLC. The tear elimination kinetic parameters AUC of F127-NLC containing 1.7%, 3.3% and 6.0% F127-NLC in rabbit eyes for 6h were 1.57, 1.79 and 2.42 times of NLC, respectively, and MRTs were 1.19, 1.31 and 1.90 times of NLC, respectively. Conclusion The addition of 6.0% F127 NLC can significantly increase the drug concentration in the tear, prolong the duration of action and reduce irritation.