Drug Distribution to Retinal Pigment Epithelium: Studies on Melanin Binding, Cellular Kinetics, and Single Photon Emission Computed Tomography/Computed Tomography Imaging
Melanin binding is known to affect the distribution and elimination of ocular drugs. The purpose of this study was to evaluate if the extent of drug uptake to primary retinal pigment epithelial (RPE) cells could be estimated based on in vitro binding studies with isolated melanin and evaluate the su...
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Published in | Molecular pharmaceutics Vol. 13; no. 9; pp. 2977 - 2986 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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United States
American Chemical Society
06.09.2016
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Abstract | Melanin binding is known to affect the distribution and elimination of ocular drugs. The purpose of this study was to evaluate if the extent of drug uptake to primary retinal pigment epithelial (RPE) cells could be estimated based on in vitro binding studies with isolated melanin and evaluate the suitability of single photon emission computed tomography/computed tomography (SPECT/CT) in studying pigment binding in vivo with pigmented and albino rats. Binding of five compounds, basic molecules timolol, chloroquine, and nadolol and acidic molecules methotrexate and 5(6)-carboxy-2′,7′-dichlorofluorescein (CDCF), was studied using isolated melanin from porcine choroid-RPE at pH 5.0 and 7.4. The uptake to primary porcine RPE cells was studied with timolol, chloroquine, methotrexate, and CDCF. The cell study setting was modeled using parameters from the in vitro binding study. In vivo kinetics of 3-[I-123]-iodochloroquine was studied by the SPECT/CT method in albino and pigmented rats. All basic compounds bound to melanin at both pH values, whereas the acidic compounds bound more at pH 5.0 than at pH 7.4. The basic compounds (chloroquine, timolol) showed significant cellular uptake, unlike the acidic compounds (methotrexate, CDCF). On the basis of the modeling, melanin binding was a major factor governing the overall drug distribution to the RPE cells. Likewise, melanin binding explained distribution of 3-[I-123]-iodochloroquine in the pigmented RPE, whereas drug accumulation was not seen in the albino rat. This study demonstrates the suitability of noninvasive SPECT/CT imaging in monitoring ocular melanin binding in vivo. These studies are a useful step toward understanding the pharmacokinetic impact of melanin binding. |
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AbstractList | Melanin binding is known to affect the distribution and elimination of ocular drugs. The purpose of this study was to evaluate if the extent of drug uptake to primary retinal pigment epithelial (RPE) cells could be estimated based on in vitro binding studies with isolated melanin and evaluate the suitability of single photon emission computed tomography/computed tomography (SPECT/CT) in studying pigment binding in vivo with pigmented and albino rats. Binding of five compounds, basic molecules timolol, chloroquine, and nadolol and acidic molecules methotrexate and 5(6)-carboxy-2′,7′-dichlorofluorescein (CDCF), was studied using isolated melanin from porcine choroid-RPE at pH 5.0 and 7.4. The uptake to primary porcine RPE cells was studied with timolol, chloroquine, methotrexate, and CDCF. The cell study setting was modeled using parameters from the in vitro binding study. In vivo kinetics of 3-[I-123]-iodochloroquine was studied by the SPECT/CT method in albino and pigmented rats. All basic compounds bound to melanin at both pH values, whereas the acidic compounds bound more at pH 5.0 than at pH 7.4. The basic compounds (chloroquine, timolol) showed significant cellular uptake, unlike the acidic compounds (methotrexate, CDCF). On the basis of the modeling, melanin binding was a major factor governing the overall drug distribution to the RPE cells. Likewise, melanin binding explained distribution of 3-[I-123]-iodochloroquine in the pigmented RPE, whereas drug accumulation was not seen in the albino rat. This study demonstrates the suitability of noninvasive SPECT/CT imaging in monitoring ocular melanin binding in vivo. These studies are a useful step toward understanding the pharmacokinetic impact of melanin binding. |
Author | Antopolsky, Maxim Latonen, Satu Manzanares, José A Schmitt, Mechthild Kidron, Heidi Urtti, Arto Hagström, Marja Rimpelä, Anna-Kaisa |
AuthorAffiliation | School of Pharmacy Department of Thermodynamics, Faculty of Physics University of Eastern Finland University of Helsinki Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy University of Valencia |
AuthorAffiliation_xml | – name: University of Eastern Finland – name: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy – name: Department of Thermodynamics, Faculty of Physics – name: University of Valencia – name: School of Pharmacy – name: University of Helsinki |
Author_xml | – sequence: 1 givenname: Anna-Kaisa surname: Rimpelä fullname: Rimpelä, Anna-Kaisa email: anna-kaisa.rimpela@helsinki.fi – sequence: 2 givenname: Mechthild surname: Schmitt fullname: Schmitt, Mechthild – sequence: 3 givenname: Satu surname: Latonen fullname: Latonen, Satu – sequence: 4 givenname: Marja surname: Hagström fullname: Hagström, Marja – sequence: 5 givenname: Maxim surname: Antopolsky fullname: Antopolsky, Maxim – sequence: 6 givenname: José A surname: Manzanares fullname: Manzanares, José A – sequence: 7 givenname: Heidi surname: Kidron fullname: Kidron, Heidi – sequence: 8 givenname: Arto surname: Urtti fullname: Urtti, Arto |
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Cites_doi | 10.1016/0014-4835(84)90104-0 10.1093/jat/29.5.339 10.3109/03602538409033561 10.1016/j.ejps.2012.03.013 10.1089/jop.1992.8.35 10.1021/acs.molpharmaceut.5b00783 10.1167/iovs.07-0214 10.1016/j.addr.2006.07.025 10.1006/excr.2000.5092 10.1211/0022357043932 10.1016/0968-0004(89)90157-6 10.1016/j.jconrel.2010.08.028 10.1016/j.colsurfb.2015.06.040 10.1007/s10450-007-9059-8 10.1167/iovs.07-0593 10.1016/S0014-4835(02)00247-6 10.1016/0006-2952(79)90326-5 10.1016/j.drudis.2007.11.002 10.1021/mp4000822 10.1007/s11095-007-9342-0 10.1006/abbi.1993.1577 10.1167/iovs.05-0945 |
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References | ref9/cit9 ref6/cit6 ref27/cit27 ref18/cit18 Trope G. E. (ref19/cit19) 1994; 29 Potts A. M. (ref4/cit4) 1995 ref11/cit11 ref25/cit25 ref16/cit16 ref23/cit23 ref14/cit14 ref8/cit8 ref5/cit5 ref2/cit2 Salazar M. (ref3/cit3) 1976; 197 Potts A. M. (ref1/cit1) 1964; 3 ref20/cit20 ref10/cit10 ref26/cit26 ref21/cit21 ref12/cit12 ref15/cit15 Rosenthal a R. (ref17/cit17) 1978; 17 ref22/cit22 ref13/cit13 ref24/cit24 ref7/cit7 |
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SubjectTerms | Animals Cells, Cultured Chloroquine - metabolism Eye - metabolism Hydrogen-Ion Concentration Iodine Radioisotopes Kinetics Melanins - metabolism Methotrexate - metabolism Nadolol - metabolism Protein Binding Rats Retinal Pigment Epithelium - metabolism Single Photon Emission Computed Tomography Computed Tomography - methods Swine Timolol - metabolism |
Title | Drug Distribution to Retinal Pigment Epithelium: Studies on Melanin Binding, Cellular Kinetics, and Single Photon Emission Computed Tomography/Computed Tomography Imaging |
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