基于立方液晶的新型载体用于眼部递送氟比洛芬，具有低刺激性和高生物利用度。
Novel vehicle based on cubosomes for ophthalmic delivery of flurbiprofen with low irritancy and high bioavailability.
机构信息
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
出版信息
Acta Pharmacol Sin. 2010 Aug;31(8):990-8. doi: 10.1038/aps.2010.98.
AIM
To develop a novel vehicle based on cubosomes as an ophthalmic drug delivery system for flurbiprofen (FB) to reduce ocular irritancy and improve bioavailability.
METHODS
FB-loaded cubosomes were prepared using hot and high-pressure homogenization. Cubosomes were then characterized by particle size, zeta potential, encapsulation efficiency, particle morphology, inner cubic structure and in vitro release. Corneal permeation was evaluated using modified Franz-type cells. Ocular irritation was then evaluated using both the Draize method and histological examination. The ocular pharmacokinetics of FB was determined using microdialysis.
RESULTS
The particle size of each cubosome formulation was about 150 nm. A bicontinuous cubic phase of cubic P-type was determined using cryo-transmission electron microscopy (cryo-TEM) observation and small angle X-ray scattering (SAXS) analysis. In vitro corneal permeation study revealed that FB formulated in cubosomes exhibited 2.5-fold (F1) and 2.0-fold (F2) increase in P(app) compared with FB PBS. In the ocular irritation test, irritation scores for each group were less than 2, indicating that all formulations exhibited excellent ocular tolerance. Histological examination revealed that neither the structure nor the integrity of the cornea was visibly affected after incubation with FB cubosomes. The AUC of FB administered as FB cubosome F2 was 486.36+/-38.93 ng.mL(-1).min.microg(-1), which was significantly higher than that of FB Na eye drops (P<0.01). Compared with FB Na eye drops, the T(max) of FB cubosome F2 was about 1.6-fold higher and the MRT was also significantly longer (P<0.001).
CONCLUSION
This novel low-irritant vehicle based on cubosomes might be a promising system for effective ocular drug delivery.
目的
开发一种基于立方液晶的新型载体作为氟比洛芬（FB）的眼部给药系统，以降低眼部刺激性并提高生物利用度。
方法
采用热高压匀浆法制备载 FB 的立方液晶。然后通过粒径、Zeta 电位、包封效率、颗粒形态、内立方结构和体外释放对立方液晶进行表征。采用改良的 Franz 型细胞评估角膜渗透。然后采用 Draize 法和组织学检查评估眼部刺激性。采用微透析法测定 FB 的眼部药代动力学。
结果
每个立方液晶制剂的粒径约为 150nm。采用冷冻传输电子显微镜（cryo-TEM）观察和小角 X 射线散射（SAXS）分析确定立方 P 型双连续立方相。体外角膜渗透研究表明，与 FB PBS 相比，FB 立方液晶制剂的 P(app)增加了 2.5 倍（F1）和 2.0 倍（F2）。在眼部刺激性试验中，各组的刺激评分均小于 2，表明所有制剂均表现出良好的眼部耐受性。组织学检查显示，用 FB 立方液晶孵育后，角膜的结构和完整性均未受到明显影响。FB 以 FB 立方液晶 F2 给药的 AUC 为 486.36+/-38.93ng·mL(-1)·min·μg(-1)，明显高于 FB Na 滴眼液（P<0.01）。与 FB Na 滴眼液相比，FB 立方液晶 F2 的 T(max)约提高 1.6 倍，MRT 也明显延长（P<0.001）。
结论
这种基于立方液晶的新型低刺激性载体可能是一种有前途的有效眼部药物传递系统。
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