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目的制备适于眼部给药的环孢素A生物黏附性纳米脂质载体,考察其在家兔眼组织的分布情况,并进行眼局部刺激性研究。方法采用熔融-乳化法制备纳米脂质载体,与生物黏附性材料泊洛沙姆407(P407)溶液混合后,得到泊洛沙姆407纳米脂质载体。运用激光粒度仪测定粒径,透射电镜观察形态,流变仪测定黏度,动态透析法研究其在人工泪液中的释药行为,HPLC测定泊洛沙姆407纳米脂质载体在家兔眼部各组织中不同时间点药物浓度,以未加入泊洛沙姆407的纳米脂质载体(CsA-NLC)及药物油滴眼液作对照,采用线性梯形法计算参数。利用家兔研究其眼局部刺激性。结果泊洛沙姆407纳米脂质载体多为类球形粒子,泊洛沙姆407包覆于纳米脂质载体的外表,其平均粒径(41.2±0.2)nm,Zeta电位(-15.2±0.21)mV,属于非牛顿流体。体外释放表明,泊洛沙姆407纳米脂质载体具有明显的缓释特征,且体外释药行为符合单指数分布模型。含6.0%泊洛沙姆407的泊洛沙姆407纳米脂质载体在角膜、房水、虹膜的AUC0-24 h分别是油滴眼液的10.75、4.45和4.62倍,是环孢素A纳米脂质载体的2.77、1.22和1.54倍,MRT分别是油滴眼液的3.28、2.26和3.46倍,是环孢素A纳米脂质载体的1.69、1.50和1.62倍。泊洛沙姆407纳米脂质载体对家兔眼部无刺激性。结论泊洛沙姆407纳米脂质载体可延长药物在眼部的作用时间,显著提高药物在眼部各组织中的浓度,减少刺激性,作为眼部给药载体具有良好的应用前景。
OBJECTIVE To prepare cyclosporin A bioadhesive nanosomes for ocular administration and investigate its distribution in ocular tissues of rabbits. Methods Nanoliposomes were prepared by melt-emulsion method and mixed with bioadhesive material Poloxamer 407 (P407) to obtain Poloxamer 407 nm lipid carrier. The particle size was measured by laser particle size analyzer, the morphology was observed by transmission electron microscopy, the viscosity was measured by rheometer, and the release behavior in artificial tear was studied by dynamic dialysis. The poloxamer 407 nm lipid carrier The drug concentrations at different time points in the tissue were compared with CsA-NLC and drug oil eye drops without poloxamer 407, and the parameters were calculated by the linear trapezoidal method. Rabbits were used to study their eye irritation. Results Poloxamer 407 nanostructured lipid nanoparticles were mostly spherical. Poloxamer 407 was coated on the surface of nanosized lipid carriers with average diameter (41.2 ± 0.2) nm and Zeta potential (-15.2 ± 0.21) mV, belonging to non-Newtonian fluid. In vitro release showed that the poloxamer 407 nanoliposomes had a sustained release profile and the in vitro release behavior was in accordance with the single exponential distribution model. Poloxamer 407 containing 6.0% poloxamer 407 nano-lipid carrier in the cornea, aqueous humor, iris AUC0-24 h were 10.75, 4.45 and 4.62 times the oil eye drops, is cyclosporine A nano 2.77, 1.22 and 1.54 times higher than that of the lipid carrier. MRT was 3.28, 2.26 and 3.46 times higher than that of the oil eye drops respectively, which were 1.69, 1.50 and 1.62 times that of the cyclosporin A nanosized lipid carrier. Poloxamer 407 nanometer lipid carrier is non-irritating to eyes of rabbits. Conclusion Poloxamer 407 nanoliposomes can prolong the action time of the drug in the eye, significantly increase the concentration of the drug in each tissue of the eye, reduce the irritation, and have good application prospect as the ophthalmic drug delivery carrier.