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Rate of Drug Coating Dissolution Determines In-Tissue Drug Retention and Durability of Biological Efficacy

Two different drug-coated balloons (DCBs) possessing different coating formulations were compared for rate of coating dissolution in vitro, in addition to tissue drug concentration and histological responses of treated vascular tissue in vivo, to determine if the rate of drug bioavailability to vasc...

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Autores principales: Granada, Juan F., Virmani, Renu, Schulz-Jander, Daniel, Tunev, Stefan, Melder, Robert J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388343/
https://www.ncbi.nlm.nih.gov/pubmed/30886750
http://dx.doi.org/10.1155/2019/9560592
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author Granada, Juan F.
Virmani, Renu
Schulz-Jander, Daniel
Tunev, Stefan
Melder, Robert J.
author_facet Granada, Juan F.
Virmani, Renu
Schulz-Jander, Daniel
Tunev, Stefan
Melder, Robert J.
author_sort Granada, Juan F.
collection PubMed
description Two different drug-coated balloons (DCBs) possessing different coating formulations were compared for rate of coating dissolution in vitro, in addition to tissue drug concentration and histological responses of treated vascular tissue in vivo, to determine if the rate of drug bioavailability to vascular tissue can impact the degree and duration of the observed pharmacological response to locally delivered drug. In vitro dissolution comparison demonstrated that a urea/paclitaxel-based coating formulation (IN.PACT™ Admiral™) released drug from solid to soluble phase at a slower and constant rate, yielding approximately 7% solubilized drug in 24 h. In contrast, a coating formulated from polysorbate/sorbitol/paclitaxel (Lutonix™) released 51% of solid phase drug to soluble phase in 1 h of dissolution with the remainder solubilizing in 24 h. In vivo evaluation of tissue drug concentration of both products showed significantly different tissue pharmacokinetic profile, with a higher concentration of paclitaxel in tissue at 90 days with a urea-based formulation excipient. Histological comparison of smooth muscle cell loss in response to drug exposure revealed contrasting trends of smooth muscle cell loss from 28 to 90 days with significantly higher response to drug observed at 90 days with the urea-based formulation. Rapid dissolution of drug from the polysorbate/sorbitol coating formulation was associated with an early increase in local cellular response to drug which diminished over 90 days with clearance of local drug from tissue. Sustained long-term drug-in-tissue concentration associated with the urea-based formulation demonstrated sustained pharmacological activity at 90 days, suggesting that slow coating dissolution provides a sustainable long-term tissue response.
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spelling pubmed-63883432019-03-18 Rate of Drug Coating Dissolution Determines In-Tissue Drug Retention and Durability of Biological Efficacy Granada, Juan F. Virmani, Renu Schulz-Jander, Daniel Tunev, Stefan Melder, Robert J. J Drug Deliv Research Article Two different drug-coated balloons (DCBs) possessing different coating formulations were compared for rate of coating dissolution in vitro, in addition to tissue drug concentration and histological responses of treated vascular tissue in vivo, to determine if the rate of drug bioavailability to vascular tissue can impact the degree and duration of the observed pharmacological response to locally delivered drug. In vitro dissolution comparison demonstrated that a urea/paclitaxel-based coating formulation (IN.PACT™ Admiral™) released drug from solid to soluble phase at a slower and constant rate, yielding approximately 7% solubilized drug in 24 h. In contrast, a coating formulated from polysorbate/sorbitol/paclitaxel (Lutonix™) released 51% of solid phase drug to soluble phase in 1 h of dissolution with the remainder solubilizing in 24 h. In vivo evaluation of tissue drug concentration of both products showed significantly different tissue pharmacokinetic profile, with a higher concentration of paclitaxel in tissue at 90 days with a urea-based formulation excipient. Histological comparison of smooth muscle cell loss in response to drug exposure revealed contrasting trends of smooth muscle cell loss from 28 to 90 days with significantly higher response to drug observed at 90 days with the urea-based formulation. Rapid dissolution of drug from the polysorbate/sorbitol coating formulation was associated with an early increase in local cellular response to drug which diminished over 90 days with clearance of local drug from tissue. Sustained long-term drug-in-tissue concentration associated with the urea-based formulation demonstrated sustained pharmacological activity at 90 days, suggesting that slow coating dissolution provides a sustainable long-term tissue response. Hindawi 2019-01-08 /pmc/articles/PMC6388343/ /pubmed/30886750 http://dx.doi.org/10.1155/2019/9560592 Text en Copyright © 2019 Juan F. Granada et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Granada, Juan F.
Virmani, Renu
Schulz-Jander, Daniel
Tunev, Stefan
Melder, Robert J.
Rate of Drug Coating Dissolution Determines In-Tissue Drug Retention and Durability of Biological Efficacy
title Rate of Drug Coating Dissolution Determines In-Tissue Drug Retention and Durability of Biological Efficacy
title_full Rate of Drug Coating Dissolution Determines In-Tissue Drug Retention and Durability of Biological Efficacy
title_fullStr Rate of Drug Coating Dissolution Determines In-Tissue Drug Retention and Durability of Biological Efficacy
title_full_unstemmed Rate of Drug Coating Dissolution Determines In-Tissue Drug Retention and Durability of Biological Efficacy
title_short Rate of Drug Coating Dissolution Determines In-Tissue Drug Retention and Durability of Biological Efficacy
title_sort rate of drug coating dissolution determines in-tissue drug retention and durability of biological efficacy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388343/
https://www.ncbi.nlm.nih.gov/pubmed/30886750
http://dx.doi.org/10.1155/2019/9560592
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