Fluorescent Penetration Enhancers Reveal Complex Interactions among the Enhancer, Drug, Solvent, and Skin

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F19%3A10400443" target="_blank" >RIV/00216208:11160/19:10400443 - isvavai.cz</a>

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=aHD5FDbp8" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=aHD5FDbp8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.molpharmaceut.8b01196" target="_blank" >10.1021/acs.molpharmaceut.8b01196</a>

Result language

angličtina

Original language name

Fluorescent Penetration Enhancers Reveal Complex Interactions among the Enhancer, Drug, Solvent, and Skin

Original language description

Skin penetration/permeation enhancers facilitate drug delivery through the skin barrier. However, the specific mechanisms that govern the enhancer interactions with the skin, drug, and donor solvent are not fully understood. We designed and synthesized fluorescent-labeled enhancers by attaching 7-nitrobenzo[c][1,2,5]doxadiazol-4-yl (NBD) groups to 6-amino-hexanoic acid esters. These NBD esters (applied at a 1% concentration) enhanced the permeation of the model drugs theophylline and hydrocortisone through human skin in vitro up to 6.6- and 3.9-times, respectively. The enhancement effects were strongly affected by the ester chain length (C8-C12) and the polarity of the donor solvent. Using high-performance liquid chromatography with fluorescence detection, no NBD esters were detected in the acceptor buffer, but their hydrolysis product, NBD acid, was detected, whereas both acid and esters were found in the skin. The enhancer hydrolysis occurred in the lower stratum corneum and epidermis; more hydrophilic NBD acid, which is an inactive enhancer, penetrated deeper. This illustrates the principle of biodegradable enhancers. The enhancer concentrations in the skin depended not only on the enhancer chain length and the donor solvent, but also on the drug used. Thus, the drug, when coapplied with the enhancer, modulates the enhancer penetration into the skin and, consequently, its effect. Finally, active (NBD-C8 ester) and inactive (NBD acid) enhancers were visualized in human skin by confocal laser scanning microscopy. Both compounds were found mostly in the stratum corneum intercellular spaces, suggesting that although both are located within the skin barrier lipids, only the active ester is able to effectively interact with the lipids, which was proved by infrared spectroscopy of enhancer-treated stratum corneum. This proof of -concept study illustrates the use of fluorescent enhancers to obtain insight into the skin penetration/permeation process; interactions among the enhancer, drug, solvent, and skin; and enhancer metabolism.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecular Pharmaceutics

ISSN

1543-8384

e-ISSN

—

Volume of the periodical

16

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

886-897

UT code for WoS article

000458085700040

EID of the result in the Scopus database

2-s2.0-85060978916