Development of a new topical treatment system for the eye

我们评估了壳聚糖包衣脂质纳米球（CS-LNS）作为一种新的局部滴眼系统，可以靶向眼后极。首先，我们用含有DiI染料的CS-LNS对白化病兔眼进行局部治疗。CS未包被的LNS作为对照。滴眼后1小时，摘除眼睛，通过共聚焦激光扫描显微镜检查DiI的积聚。DiI在结膜、角膜和前巩膜-脉络膜-视网膜中有明显蓄积，而在后巩膜-脉络膜-视网膜中蓄积较少。接下来，我们使用含有环孢霉素的CS-LNS作为白化病兔眼睛的局部治疗。滴眼液后1小时，摘除眼睛，并通过HPLC测量眼睛以下部分中的环孢霉素浓度：结膜、角膜、虹膜、房水、透镜玻璃体、前巩膜-脉络膜-视网膜和后巩膜-脉络膜-视网膜。我们在结膜和角膜中发现了显著水平的环孢素。在巩膜-脉络膜-视网膜前部， ...更多信息 结膜和角膜中的药物浓度相对较低。眼后段较低，虹膜、房水、透镜和玻璃体均未检测到环孢素。这些结果表明，CS-LNS的药物释放途径是从结膜经结膜到巩膜。通过角膜的路径可能不是主要路径。本研究通过观察泼尼松龙对实验性自身免疫性葡萄膜视网膜炎（EAU）细胞因子、趋化因子及其受体基因表达的影响，为眼内炎症的治疗寻找新的靶向分子。用cDNA微阵列进行基因表达分析，所述cDNA微阵列含有编码细胞因子和趋化因子及其受体的基因的117个单独的转录物（29个细胞因子/34个细胞因子受体; 33个趋化因子/21个趋化因子受体）。在每个时间点进行泼尼松龙处理的和安慰剂处理的EAU小鼠之间的表达的比较。基于表达谱将基因分类成簇，以阐明处理后的基因调控模式。基因芯片的系统聚类分析显示，EAU治疗后基因表达变化呈现出4种模式：平坦型、山地型、大下坡型和小下坡型。这些发现可能为确定眼部炎症的新治疗靶点开辟了新途径。少

We evaluated chitosan-coated lipid nanosphere (CS-LNS) as a new topical eye drop system which can target the posterior pole of the eye. First, we did topical treatment on eyes of albino rabbit with CS-LNS containing DiI dye. CS-non-coated LNS was served as control. 1 hour after eye drops, eyes were enucleated and accumulation of DiI was examined by confocal laser scanning microscopy. DiI significantly accumulated in conjunctiva, cornea and anterior sclera-choroid-retina, but less in posterior sclera-choroid-retina. Next, we used CS-LNS containing cyclosporine as a topical treatment on eyes of albino rabbit. 1 hour after eye drops, eyes were enucleated and concentration of cyclosporine in following parts of the eyes, conjunctiva, cornea, iris, aqueous humor, lens vitreous, anterior sclera-choroid-retina and posterior sclera-choroid-retina, was measured by HPLC. We found significant levels of cyclosporine in conjunctiva and cornea. In anterior sclera-choroid-retina, the concentration of … More the drug was relatively lower than that of in conjunctiva and cornea. In posterior segment of the eye, it was much less. In iris, aqueous humor, lens and vitreous, we could not detect cyclosporine. These results suggested that drug delivery pathway with using CS-LNS was from conjunctiva to sclera via tenon. Pathway through cornea might not be a main road. Our study demonstrated that CS-LNS can be a new topical delivery system targeting to the posterior segment of the eye.To search a new targeting molecule for the treatment of intraocular inflammation, we investigated changes in gene expression of cytokines and chemokines and their receptors after systemic prednisolone treatment in experimental autoimmune uveoretinitis (EAU). Gene expression analysis was conducted with the cDNA microarray, which contains 117 individual transcripts encoding the genes of the cytokines and chemokines and their receptors (29 cytokines/34 cytokine receptors; 33 chemokines/21 chemokine receptors). Comparisons of expression between predonisolone-treated and placebo-treated EAU mice at each time point were performed. The genes were sorted into clusters based on expression profiles to clarify the gene regulation pattern after treatment. Hierarchical cluster analysis of the microarray demonstrated that gene expression changes in EAU after treatment showed four patterns: flat, mountain, large downhill, and small downhill. These findings may open a new avenue to identify new therapeutic targets in ocular inflammation. Less