地塞米松纳米立方液晶眼用制剂家兔房水药代动力学
Ocular pharmacokinetics of dexamethasone cubosomes in rabbit aqueous humor
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摘要: 目的 ： 以地塞米松（DEX）为模型药物制备眼用纳米立方液晶眼用制剂，并对其家兔房水药代动力学进行了考察。 方法 ： 采用高压均质法制备DEX纳米立方液晶，激光粒度测定仪测定粒径，低温透射电镜观察粒子的微观形态；Draize评分法评价制剂的眼部刺激性；采用微渗析法评价家兔的房水药代动力学。 结果 ： DEX纳米立方液晶平均粒径约200 nm，低温透射电镜可见其清晰的立方体结构。Draize评分结果显示，该制剂对家兔眼部无刺激性。房水药代动力学结果显示，DEX纳米立方液晶制剂组AUC0→240，c max 均显著高于市售溶液剂组，且处方1（F1，10%脂质含量）和处方2（F2，20%脂质含量）的AUC0→240分别是市售溶液剂的1.8倍和2.9倍（P<0.05）。 结论 ： DEX纳米立方液晶眼用制剂能够显著提高房水药物浓度，改善药物在眼部组织的生物利用度。Abstract: Aim ：To prepare novel cubosome system for effective ocular drug delivery with dexamethasone(DEX) as model drug，and investigate its pharmacokinetic profile in rabbit aqueous humor. Methods ：DEX cubosomes was prepared by the method of high-pressure homogenization，and its particle size was determined by the laser particle sizer，and the microstructure observed by cryo-TEM.In addition，Draize method was used to evaluate the ocular irritation of DEX cubosomes. Finally，aqueous humor microdialysis was utilized to evaluate its pharmacokinetics in rabbits. Results ：Average diameter of DEX cubosomes was about 200 nm，and the cubic structure of the particles was evident under the cryo-TEM.It was indicated by Draize scores that this dosage form exhibited excellent ocular tolerance.Results of pharmacokinetic profiles in aqueous humor showed that AUC 0→240 and c max of the rabbit group administered with DEX cubosomes were significantly higher than those of the control group(DEX sodium phosphate eye drops)，with AUC0→240 of the formulation F1(10% oil content) and F2(20% oil content) is being about 1.8 and 2.9 times higher than those of the control group，respectively(P<0.05). Conclusion ：The novel ocular drug delivery system of DEX cubosomes was capable of increasing significantly the drug concentration in aqueous humor，and improving the ocular bioavailability.
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Keywords:
- dexamethasone /
- cubosomes /
- microdialysis /
- aqueous humor /
- pharmacokinetics
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