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Transfersome Encapsulated with the R-carvedilol Enantiomer for Skin Cancer Chemoprevention

The R-carvedilol enantiomer, present in the racemic mixture of the chiral drug carvedilol, does not bind to the β-adrenergic receptors, but exhibits skin cancer preventive activity. For skin delivery, R-carvedilol-loaded transfersomes were prepared using various ratios of drug, lipids, and surfactan...

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Autores principales: Shamim, Md Abdullah, Shahid, Ayaz, Sardar, Pabitra K., Yeung, Steven, Reyes, Jeremiah, Kim, Jenny, Parsa, Cyrus, Orlando, Robert, Wang, Jeffrey, Kelly, Kristen M., Meyskens, Frank L., Andresen, Bradley T., Huang, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10005314/
https://www.ncbi.nlm.nih.gov/pubmed/36903807
http://dx.doi.org/10.3390/nano13050929
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author Shamim, Md Abdullah
Shahid, Ayaz
Sardar, Pabitra K.
Yeung, Steven
Reyes, Jeremiah
Kim, Jenny
Parsa, Cyrus
Orlando, Robert
Wang, Jeffrey
Kelly, Kristen M.
Meyskens, Frank L.
Andresen, Bradley T.
Huang, Ying
author_facet Shamim, Md Abdullah
Shahid, Ayaz
Sardar, Pabitra K.
Yeung, Steven
Reyes, Jeremiah
Kim, Jenny
Parsa, Cyrus
Orlando, Robert
Wang, Jeffrey
Kelly, Kristen M.
Meyskens, Frank L.
Andresen, Bradley T.
Huang, Ying
author_sort Shamim, Md Abdullah
collection PubMed
description The R-carvedilol enantiomer, present in the racemic mixture of the chiral drug carvedilol, does not bind to the β-adrenergic receptors, but exhibits skin cancer preventive activity. For skin delivery, R-carvedilol-loaded transfersomes were prepared using various ratios of drug, lipids, and surfactants, and characterized for particle size, zeta potential, encapsulation efficiency, stability, and morphology. Transfersomes were compared for in vitro drug release and ex vivo skin penetration and retention. Skin irritation was evaluated by viability assay on murine epidermal cells and reconstructed human skin culture. Single-dose and repeated-dose dermal toxicity was determined in SKH-1 hairless mice. Efficacy was evaluated in SKH-1 mice exposed to single or multiple ultraviolet (UV) radiations. Transfersomes released the drug at a slower rate, but significantly increased skin drug permeation and retention compared with the free drug. The transfersome with a drug–lipid–surfactant ratio of 1:3:0.5 (T-RCAR-3) demonstrated the highest skin drug retention and was selected for further studies. T-RCAR-3 at 100 µM did not induce skin irritation in vitro and in vivo. Topical treatment with T-RCAR-3 at 10 µM effectively attenuated acute UV-induced skin inflammation and chronic UV-induced skin carcinogenesis. This study demonstrates feasibility of using R-carvedilol transfersome for preventing UV-induced skin inflammation and cancer.
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spelling pubmed-100053142023-03-11 Transfersome Encapsulated with the R-carvedilol Enantiomer for Skin Cancer Chemoprevention Shamim, Md Abdullah Shahid, Ayaz Sardar, Pabitra K. Yeung, Steven Reyes, Jeremiah Kim, Jenny Parsa, Cyrus Orlando, Robert Wang, Jeffrey Kelly, Kristen M. Meyskens, Frank L. Andresen, Bradley T. Huang, Ying Nanomaterials (Basel) Article The R-carvedilol enantiomer, present in the racemic mixture of the chiral drug carvedilol, does not bind to the β-adrenergic receptors, but exhibits skin cancer preventive activity. For skin delivery, R-carvedilol-loaded transfersomes were prepared using various ratios of drug, lipids, and surfactants, and characterized for particle size, zeta potential, encapsulation efficiency, stability, and morphology. Transfersomes were compared for in vitro drug release and ex vivo skin penetration and retention. Skin irritation was evaluated by viability assay on murine epidermal cells and reconstructed human skin culture. Single-dose and repeated-dose dermal toxicity was determined in SKH-1 hairless mice. Efficacy was evaluated in SKH-1 mice exposed to single or multiple ultraviolet (UV) radiations. Transfersomes released the drug at a slower rate, but significantly increased skin drug permeation and retention compared with the free drug. The transfersome with a drug–lipid–surfactant ratio of 1:3:0.5 (T-RCAR-3) demonstrated the highest skin drug retention and was selected for further studies. T-RCAR-3 at 100 µM did not induce skin irritation in vitro and in vivo. Topical treatment with T-RCAR-3 at 10 µM effectively attenuated acute UV-induced skin inflammation and chronic UV-induced skin carcinogenesis. This study demonstrates feasibility of using R-carvedilol transfersome for preventing UV-induced skin inflammation and cancer. MDPI 2023-03-03 /pmc/articles/PMC10005314/ /pubmed/36903807 http://dx.doi.org/10.3390/nano13050929 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shamim, Md Abdullah
Shahid, Ayaz
Sardar, Pabitra K.
Yeung, Steven
Reyes, Jeremiah
Kim, Jenny
Parsa, Cyrus
Orlando, Robert
Wang, Jeffrey
Kelly, Kristen M.
Meyskens, Frank L.
Andresen, Bradley T.
Huang, Ying
Transfersome Encapsulated with the R-carvedilol Enantiomer for Skin Cancer Chemoprevention
title Transfersome Encapsulated with the R-carvedilol Enantiomer for Skin Cancer Chemoprevention
title_full Transfersome Encapsulated with the R-carvedilol Enantiomer for Skin Cancer Chemoprevention
title_fullStr Transfersome Encapsulated with the R-carvedilol Enantiomer for Skin Cancer Chemoprevention
title_full_unstemmed Transfersome Encapsulated with the R-carvedilol Enantiomer for Skin Cancer Chemoprevention
title_short Transfersome Encapsulated with the R-carvedilol Enantiomer for Skin Cancer Chemoprevention
title_sort transfersome encapsulated with the r-carvedilol enantiomer for skin cancer chemoprevention
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10005314/
https://www.ncbi.nlm.nih.gov/pubmed/36903807
http://dx.doi.org/10.3390/nano13050929
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