Synthesis of Taurine-fluorescein Conjugate and Evaluation of Its Retina-targeted Efficiency in Vitro

Overview

Journal Acta Pharm Sin B

Publisher Elsevier

Specialty Pharmacology

Date 2015 Nov 19

PMID 26579416

Citations 1

Authors

Meihong Huang

Jiaqi Song

BingZheng Lu

Huizhi Huang

Yizhen Chen

Wei Yin

Wenbo Zhu

Xinwen Su

Chuanbin Wu

Haiyan Hu

Affiliations

Soon will be listed here.

Abstract

In this work, retinal penetration of fluorescein was achieved in vitro by covalent attachment of taurine to fluorescein, yielding the F-Tau conjugate. Nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS) were used to confirm the successful synthesis of F-Tau. The cellular uptake of F-Tau in adult retinal pigment epithelial cells (ARPE-19) and human retinal microvascular endothelial cells (hRMECs) was visualized via confocal scanning microscopy. The results indicated an improvement of solubility and a reduction of logP of F-Tau compared with fluorescein. As compared with fluorescein, F-Tau showed little toxicity, and was retained longer by cells in uptake experiments. F-Tau also displayed higher transepithelial permeabilities than fluorescein in ARPE-19 and hRMECs monolayer cells (P<0.05). These results showed that taurine may be a useful ligand for targeting small-molecule hydrophobic pharmaceuticals into the retina.

Citing Articles

Preparation and characterization of bear bile-loaded pH sensitive gel eye drops for ocular drug delivery.

Ni X, Guo Q, Zou Y, Xuan Y, Mohammad I, Ding Q Iran J Basic Med Sci. 2020; 23(7):922-929.

PMID: 32774815 PMC: 7395188. DOI: 10.22038/IJBMS.2020.45386.10562.

References

Tomi M, Terayama T, Isobe T, Egami F, Morito A, Kurachi M . Function and regulation of taurine transport at the inner blood-retinal barrier. Microvasc Res. 2006; 73(2):100-6. DOI: 10.1016/j.mvr.2006.10.003. View

Gillies M, Su T, Naidoo D . Electrical resistance and macromolecular permeability of retinal capillary endothelial cells in vitro. Curr Eye Res. 1995; 14(6):435-42. DOI: 10.3109/02713689509003753. View

Geggel H, Ament M, Heckenlively J, Martin D, Kopple J . Nutritional requirement for taurine in patients receiving long-term parenteral nutrition. N Engl J Med. 1985; 312(3):142-6. DOI: 10.1056/NEJM198501173120302. View

Hornof M, Toropainen E, Urtti A . Cell culture models of the ocular barriers. Eur J Pharm Biopharm. 2005; 60(2):207-25. DOI: 10.1016/j.ejpb.2005.01.009. View

Ausayakhun S, Yuvaves P, Ngamtiphakom S, Prasitsilp J . Treatment of cytomegalovirus retinitis in AIDS patients with intravitreal ganciclovir. J Med Assoc Thai. 2006; 88 Suppl 9:S15-20. View

Heinamaki A, Muhonen A, PIHA R . Taurine and other free amino acids in the retina, vitreous, lens, iris-ciliary body, and cornea of the rat eye. Neurochem Res. 1986; 11(4):535-42. DOI: 10.1007/BF00965323. View

Tretiach M, van Driel D, Gillies M . Transendothelial electrical resistance of bovine retinal capillary endothelial cells is influenced by cell growth patterns: an ultrastructural study. Clin Exp Ophthalmol. 2003; 31(4):348-53. DOI: 10.1046/j.1442-9071.2003.00670.x. View

Hansen S . The role of taurine in diabetes and the development of diabetic complications. Diabetes Metab Res Rev. 2001; 17(5):330-46. DOI: 10.1002/dmrr.229. View

Bridges C, Ola M, Prasad P, Ganapathy V, Smith S . Regulation of taurine transporter expression by NO in cultured human retinal pigment epithelial cells. Am J Physiol Cell Physiol. 2001; 281(6):C1825-36. PMC: 4637984. DOI: 10.1152/ajpcell.2001.281.6.C1825. View

10.

Duvvuri S, Majumdar S, Mitra A . Drug delivery to the retina: challenges and opportunities. Expert Opin Biol Ther. 2003; 3(1):45-56. DOI: 10.1517/14712598.3.1.45. View

11.

Hughes P, Olejnik O, Chang-Lin J, Wilson C . Topical and systemic drug delivery to the posterior segments. Adv Drug Deliv Rev. 2005; 57(14):2010-32. DOI: 10.1016/j.addr.2005.09.004. View

12.

De Luca G, Calpona P, Caponetti A, Romano G, Di Benedetto A, Cucinotta D . Taurine and osmoregulation: platelet taurine content, uptake, and release in type 2 diabetic patients. Metabolism. 2001; 50(1):60-4. DOI: 10.1053/meta.2001.19432. View

13.

Tang F, Ouyang H, Yang J, Borchardt R . Bidirectional transport of rhodamine 123 and Hoechst 33342, fluorescence probes of the binding sites on P-glycoprotein, across MDCK-MDR1 cell monolayers. J Pharm Sci. 2004; 93(5):1185-94. DOI: 10.1002/jps.20046. View

14.

Tornquist P, Alm A . Carrier-mediated transport of amino acids through the blood-retinal and the blood-brain barriers. Graefes Arch Clin Exp Ophthalmol. 1986; 224(1):21-5. DOI: 10.1007/BF02144127. View

15.

Cunha-Vaz J . The blood-ocular barriers: past, present, and future. Doc Ophthalmol. 1997; 93(1-2):149-57. DOI: 10.1007/BF02569055. View

16.

Gao J, Wang P, Giese R . Xanthamide fluorescent dyes. Anal Chem. 2003; 74(24):6397-401. DOI: 10.1021/ac020368+. View

17.

Perumal O, Inapagolla R, Kannan S, Kannan R . The effect of surface functionality on cellular trafficking of dendrimers. Biomaterials. 2008; 29(24-25):3469-76. DOI: 10.1016/j.biomaterials.2008.04.038. View

18.

Militante J, Lombardini J . Age-related retinal degeneration in animal models of aging: possible involvement of taurine deficiency and oxidative stress. Neurochem Res. 2004; 29(1):151-60. DOI: 10.1023/b:nere.0000010444.97959.1b. View

19.

Del Amo E, Urtti A . Current and future ophthalmic drug delivery systems. A shift to the posterior segment. Drug Discov Today. 2008; 13(3-4):135-43. DOI: 10.1016/j.drudis.2007.11.002. View

20.

Campbell M, Humphries P . The blood-retina barrier: tight junctions and barrier modulation. Adv Exp Med Biol. 2013; 763:70-84. View