In vivo biodistribution of topical low molecular weight heparin-taurocholate in a neovascularized mouse cornea

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英文篇名：In vivo biodistribution of topical low molecular weight heparin-taurocholate in a neovascularized mouse cornea 作者：Chan ; Hee ; Moon ; Ji ; Yun ; Lee ; Eun ; Soon ; Kim ; Jin ; Hyoung ; Park ; Sang-Yeob ; Kim ; Jae ; Yong ; Kim ; Hungwon ; Tchah 英文作者：Chan Hee Moon;Ji Yun Lee;Eun Soon Kim;Jin Hyoung Park;Sang-Yeob Kim;Jae Yong Kim;Hungwon Tchah;Department of Ophthalmology,Asan Medical Center,University of Ulsan College of Medicine;Research Institute for Biomacromolecules,University of Ulsan College of Medicine,Asan Medical Center;Department of Convergence Medicine,University of Ulsan College of Medicine,Asan Medical Center; 英文关键词：corneal neovascularization;;in vivo optical imaging;;low-molecular weight heparin;;ocular biodistribution 中文刊名：GYZZ 英文刊名：国际眼科杂志(英文版) 机构：Department of Ophthalmology,Asan Medical Center,University of Ulsan College of Medicine;Research Institute for Biomacromolecules,University of Ulsan College of Medicine,Asan Medical Center;Department of Convergence Medicine,University of Ulsan College of Medicine,Asan Medical Center; 出版日期：2018-09-06 10:55 出版单位：International Journal of Ophthalmology 年：2018 期：v.11 基金：Supported by a grant(No.2016-7026)from the Asan Institute for Life Science,Seoul,Republic of Korea 语种：英文; 页：GYZZ201809002 页数：5 CN：09 分类号：5-9

摘要

AIM: To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin(LHT7) in a neovascularized mouse cornea using an in vivo optical imaging system. METHODS: A total of 10 eyes of 6 to 8-week-old BALB/c mice were analyzed. Corneal neovascularization(CoNV) was induced in the inferior cornea(IC) of each animal by penetrating the stroma with two interrupted sutures. The development of CoNV was verified after one week and the area of each neovascularized region was measured. A near-infrared fluorescent probe of 20 μmol/L Cy5.5 labeled LHT7(LHT7-Cy5.5) in 0.02 mL solution was topically instilled onto the cornea in the experimental group(n=5). Free-Cy5.5 of 20 μmol/L in 0.02 mL was instilled in the control group(n=5). In vivo optical images were obtained before instillation and 5 min, 2, 4, and 6 h after instillation. The intensities were separately measured at the superior cornea(SC) and the IC. RESULTS: The mean CoNV areas were 1.97±0.17 mm~2 and 1.92±0.96 mm~2 in the experimental and control groups, respectively(P=0.832). The SC remained normal in all 10 subject animals. The IC intensity of the LHT7-Cy5.5 was greater than the SC intensity at 5 min(P=0.038), 2 h(P=0.041), and 4 h(P=0.041) after application. The IC intensity fell to less than half of its initial value(42.9%±8.6%) at 6 h in the experimental group. In the control mice, here were no significant differences in the free-Cy5.5 intensity between the IC and SC. CONCLUSION: Topically administered LHT7 shows a high biodistribution in CoNV areas for 4 h and should be reapplied accordingly to maintain its effects. In vivo optical imaging can be a useful tool for evaluating the ocular biodistribution of a drug in an animal model.
        AIM: To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin(LHT7) in a neovascularized mouse cornea using an in vivo optical imaging system. METHODS: A total of 10 eyes of 6 to 8-week-old BALB/c mice were analyzed. Corneal neovascularization(CoNV) was induced in the inferior cornea(IC) of each animal by penetrating the stroma with two interrupted sutures. The development of CoNV was verified after one week and the area of each neovascularized region was measured. A near-infrared fluorescent probe of 20 μmol/L Cy5.5 labeled LHT7(LHT7-Cy5.5) in 0.02 mL solution was topically instilled onto the cornea in the experimental group(n=5). Free-Cy5.5 of 20 μmol/L in 0.02 mL was instilled in the control group(n=5). In vivo optical images were obtained before instillation and 5 min, 2, 4, and 6 h after instillation. The intensities were separately measured at the superior cornea(SC) and the IC. RESULTS: The mean CoNV areas were 1.97±0.17 mm~2 and 1.92±0.96 mm~2 in the experimental and control groups, respectively(P=0.832). The SC remained normal in all 10 subject animals. The IC intensity of the LHT7-Cy5.5 was greater than the SC intensity at 5 min(P=0.038), 2 h(P=0.041), and 4 h(P=0.041) after application. The IC intensity fell to less than half of its initial value(42.9%±8.6%) at 6 h in the experimental group. In the control mice, here were no significant differences in the free-Cy5.5 intensity between the IC and SC. CONCLUSION: Topically administered LHT7 shows a high biodistribution in CoNV areas for 4 h and should be reapplied accordingly to maintain its effects. In vivo optical imaging can be a useful tool for evaluating the ocular biodistribution of a drug in an animal model.

引文

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