Whole-Eye Perfusion Model for Screening of the Ocular Formulations via Confocal Laser Scanning Microscopy.
Whole-Eye Perfusion Model for Screening of the Ocular Formulations via Confocal Laser Scanning Microscopy.
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DOI：
10.1208/s12249-019-1493-x
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发表时间：
2019-09-12
影响因子：
3.3
通讯作者：
Singh M
中科院分区：
文献类型：
--
作者：
Kutlehria S;Bagde A;Patel N;Singh M
各种生理、解剖障碍使得眼部给药非常具有挑战性。因此，需要更好的体外筛选模型来快速筛选制剂。在这项研究中，设计了一个简单的全眼灌流模型，并将其应用于利用激光共聚焦扫描显微镜筛选跨全厚角膜的靶向制剂。采用溶剂扩散挥发法制备了聚乙二醇胆钙基整合素靶向香豆素-6胶束(TC6M)和非靶向香豆素-6胶束(NTC6M)。NTC6M和TC6M的粒径分别为23.5±5 nm和28.5±6 nm，渗透压为294~300mOsml/kg。利用猪眼建立了全眼血流灌注模型。将TC6M和NTC6M分别滴入切除的猪眼和新西兰兔的眼内。摘除实验眼的角膜；用共聚焦显微镜分析香豆素-6在角膜中的渗透性。香豆素-6胶束的粒径小于50 nm。NTC6M制剂在猪眼和兔角膜中的渗透率分别达到500μm和50μm。然而，TC6M制剂表现出更好的保留力，因为在猪眼和兔眼的上层观察到更高的荧光强度，最深可达50μm，最深可达20μm。因此，成功地证明了全眼灌流模型在制剂初步筛选中的适用性。全眼灌注模型与共聚焦显微镜相结合，有可能成为快速筛选和优化各种眼科制剂的有效工具。
Various physiological, anatomical barriers make ocular drug delivery very challenging. Hence, better in vitro screening models are needed for rapid screening of the formulations. In this study, a simple whole-eye perfusion model was designed and its application was explored for screening targeted formulation across the full-thickness cornea using confocal laser scanning microscopy. PEG-cholecalciferol-based integrin targeted coumarin-6 micelles (TC6M) and non-targeted coumarin-6 micelles (NTC6M) were developed by solvent diffusion evaporation technique. The formulations NTC6M and TC6M had particles size 23.5 ± 5 nm and 28.5 ± 6 nm respectively and osmolality of 294–300 mOsml/Kg. The whole-eye perfusion model was developed using porcine eye. TC6M and NTC6M were instilled on the excised porcine eyes as well as in the eyes of NZW rabbits. Corneas were excised from the experimental eyes; coumarin-6 penetration across the corneas was analyzed using confocal microscope. Coumarin-6-loaded micelles had particle size below 50 nm. NTC6M formulations showed penetration to the deeper layers up to 500 μm porcine eyes and up to 50 μm in rabbit corneas. However, TC6M formulations exhibited superior retention, as higher fluorescent intensities were observed in upper layers up to 50 μm depth in the porcine eye and 20 μm depth in rabbit eye. Hence, applicability of whole-eye perfusion model in preliminary screening of the formulations was successfully demonstrated. Whole-eye perfusion model when combined with confocal microscopy has potential to be used as an efficient tool for rapid screening and optimization of various ophthalmic formulations.
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DOI：
10.1016/j.ejpb.2014.05.009
发表时间：
2014-09-01
影响因子：
4.9
作者：
Dutescu, R. M.;Panfil, C.;Schrage, N.
通讯作者：
Schrage, N.
影响因子：
3.8
作者：
RICHMAN, JB;TANGLIU, DDS
通讯作者：
TANGLIU, DDS
影响因子：
1.8
作者：
Schulz, D;Iliev, ME;Goldblum, D
通讯作者：
Goldblum, D
影响因子：
4.1
作者：
Dave, Vivek;Paliwal, Sarvesh
通讯作者：
Paliwal, Sarvesh
影响因子：
4.9
作者：
Morrison, Peter W. J.;Connon, Che J.;Khutoryanskiy, Vitaliy V.
通讯作者：
Khutoryanskiy, Vitaliy V.