Topical Diclofenac-Loaded Liposomes Ameliorate Laser-Induced Choroidal Neovascularization in Mice and Non-Human Primates

脉络膜新生血管 双氯芬酸 脂质体 狨猴 眼药水 化学 药理学 眼科 病变 视网膜 医学 麻醉 生物 病理 生物化学 古生物学
作者
Masamitsu Shimazawa,Yuki Inoue,Tomomi Masuda,Risako Onodera,Kohei Tahara,Yoshitaka Shimizu,Yasuhiko Mibe,Kazuhiro Tsuruma,Hirofumi Takeuchi,Hideaki Hara
出处
期刊:Current Neurovascular Research [Bentham Science]
卷期号:14 (1): 46-52 被引量:11
标识
DOI:10.2174/1567202614666161104115440
摘要

This study aimed to evaluate the effect of liposomes loaded with diclofenac, a potent cyclooxygenase (COX)-1 and COX-2 inhibitor, on laser-induced choroidal neovascularization (CNV) in mice and non-human primates (common marmosets). CNV was induced by laser irradiation on the unilateral or bilateral eye of each mouse or common marmoset, respectively, under anesthesia. The CNV was visualized using fluorescence labeling with intravenous injection of fluoresceinconjugated dextran (molecular weight = 2,000 kDa), and quantified in the retinal pigment epithelia (RPE)–choroidal flatmounts. Diclofenac-loaded liposome or diclofenac ophthalmic solution was instillated to the eye surface daily for 14 days and 21 days in mice and common marmosets, respectively. In the mouse CNV model, 0.1% diclofenac-loaded liposome eye drops administered four times a day (q.i.d.) significantly reduced CNV formation in the RPE–choroidal flatmounts compared with those in empty liposome eye drops. Diclofenac-loaded liposome (0.1%) eye drops, administered once a day (s.i.d.), twice a day (b.i.d.), and three times a day (t.i.d.), also reduced CNV formation in a frequency-dependent manner. Furthermore, diclofenac-loaded liposome (0.03% and 0.1%) eye drops administered t.i.d. reduced CNV formation in a dose-dependent manner, significantly so at 0.1%. In the common marmoset CNV model, late hyperfluorescence and leakage by fluorescein angiograms was observed within or beyond the lesion borders at 17 days after laser irradiation, and diclofenac-loaded liposome eye drops (0.1% t.i.d.) tended to attenuate the late hyperfluorescence and leakage. Diclofenac-loaded liposomes had significantly reduced CNV formation in the RPE– choroidal flatmounts at 21 days after laser irradiation. In conclusion, diclofenac-loaded liposome eye drops enhance penetration to the RPE–choroid, and reduce the CNV formation. These results suggest that a drug-loaded liposome is a useful tool for drug delivery into the posterior segment of the eye. Keywords: Age-related macular degeneration, eye drop, choroidal neovascularization, fluorescein angiograms, diclofenac, liposome, mice, primates.
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