Novel vehicle based on cubosomes for ophthalmic delivery of flurbiprofen with low irritancy and high bioavailability  

作　　者：Shun HAN Jin-qiu SHEN Yong GAN Hai-ming GENG Xin-xin ZHANG Chun-liu ZHU Li GAN 

机构地区：[1]Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China [2]School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China [3]Wuhan Wuyao Science & Technology Co Ltd, Wuhan 430033, China

出　　处：《Acta Pharmacologica Sinica》2010年第8期990-998,共9页中国药理学报（英文版）

摘　　要：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-Ioaded 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 Papp 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-m·L-1.min.μg-1, which was significantly higher than that of FB Na eye drops （P〈O.01）. Compared with FB Na eye drops, the Tmax 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.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-Ioaded 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 Papp 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-m·L-1.min.μg-1, which was significantly higher than that of FB Na eye drops （P〈O.01）. Compared with FB Na eye drops, the Tmax 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.

关 键 词：FLURBIPROFEN CUBOSOMES Ocu!ar drug delive!Y systems cornea! Permeability Ocular irritation 

分 类 号：TQ423[化学工程] S859.796[农业科学—临床兽医学]