Mechanisms of cellular retention of melanin bound drugs: Experiments and computational modeling.
Autor: | Bahrpeyma S; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, Finland; Faculty of Pharmacy, University of Helsinki, 00014, University of Helsinki, Finland. Electronic address: sina.bahrpeyma@uef.fi., Reinisalo M; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, Finland., Hellinen L; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, Finland., Auriola S; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, Finland., Del Amo EM; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, Finland., Urtti A; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, Finland; Faculty of Pharmacy, University of Helsinki, 00014, University of Helsinki, Finland; Institute of Chemistry, St. Petersburg State University, Petergoff, Russian Federation. Electronic address: arto.urtti@uef.fi. |
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Jazyk: | angličtina |
Zdroj: | Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2022 Aug; Vol. 348, pp. 760-770. Date of Electronic Publication: 2022 Jun 25. |
DOI: | 10.1016/j.jconrel.2022.05.059 |
Abstrakt: | Melanin binding of drugs is known to increase drug concentrations and retention in pigmented eye tissues. Even though the correlation between melanin binding in vitro and exposure to pigmented eye in vivo has been shown, there is a discrepancy between rapid drug release from melanin particles in vitro and the long in vivo retention in the pigmented tissues. We investigated mechanisms and kinetics of pigment-related drug retention experimentally using isolated melanin particles from porcine retinal pigment epithelium and choroid, isolated porcine eye melanosomes, and re-pigmented ARPE-19 cells in a dynamic flow system. The experimental studies were supplemented with kinetic simulations. Affinity and capacity of levofloxacin, terazosin, papaverine, and timolol binding to melanin revealed K (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.) |
Databáze: | MEDLINE |
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