Cargando…

The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo

Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities....

Descripción completa

Detalles Bibliográficos
Autores principales: Calienni, Maria Natalia, Maza Vega, Daniela, Temprana, C. Facundo, Izquierdo, María Cecilia, Ybarra, David E., Bernabeu, Ezequiel, Moretton, Marcela, Alvira, Fernando C., Chiappetta, Diego, Alonso, Silvia del Valle, Prieto, María Jimena, Montanari, Jorge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912039/
https://www.ncbi.nlm.nih.gov/pubmed/33535434
http://dx.doi.org/10.3390/pharmaceutics13020186
_version_ 1783656483317088256
author Calienni, Maria Natalia
Maza Vega, Daniela
Temprana, C. Facundo
Izquierdo, María Cecilia
Ybarra, David E.
Bernabeu, Ezequiel
Moretton, Marcela
Alvira, Fernando C.
Chiappetta, Diego
Alonso, Silvia del Valle
Prieto, María Jimena
Montanari, Jorge
author_facet Calienni, Maria Natalia
Maza Vega, Daniela
Temprana, C. Facundo
Izquierdo, María Cecilia
Ybarra, David E.
Bernabeu, Ezequiel
Moretton, Marcela
Alvira, Fernando C.
Chiappetta, Diego
Alonso, Silvia del Valle
Prieto, María Jimena
Montanari, Jorge
author_sort Calienni, Maria Natalia
collection PubMed
description Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems were the most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformable liposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can be loaded in several delivery systems for topical application. These findings may be also useful for the consideration of topical delivery of other drugs with a low water solubility.
format Online
Article
Text
id pubmed-7912039
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79120392021-02-28 The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo Calienni, Maria Natalia Maza Vega, Daniela Temprana, C. Facundo Izquierdo, María Cecilia Ybarra, David E. Bernabeu, Ezequiel Moretton, Marcela Alvira, Fernando C. Chiappetta, Diego Alonso, Silvia del Valle Prieto, María Jimena Montanari, Jorge Pharmaceutics Article Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems were the most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformable liposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can be loaded in several delivery systems for topical application. These findings may be also useful for the consideration of topical delivery of other drugs with a low water solubility. MDPI 2021-02-01 /pmc/articles/PMC7912039/ /pubmed/33535434 http://dx.doi.org/10.3390/pharmaceutics13020186 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Calienni, Maria Natalia
Maza Vega, Daniela
Temprana, C. Facundo
Izquierdo, María Cecilia
Ybarra, David E.
Bernabeu, Ezequiel
Moretton, Marcela
Alvira, Fernando C.
Chiappetta, Diego
Alonso, Silvia del Valle
Prieto, María Jimena
Montanari, Jorge
The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo
title The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo
title_full The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo
title_fullStr The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo
title_full_unstemmed The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo
title_short The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo
title_sort topical nanodelivery of vismodegib enhances its skin penetration and performance in vitro while reducing its toxicity in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912039/
https://www.ncbi.nlm.nih.gov/pubmed/33535434
http://dx.doi.org/10.3390/pharmaceutics13020186
work_keys_str_mv AT caliennimarianatalia thetopicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT mazavegadaniela thetopicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT tempranacfacundo thetopicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT izquierdomariacecilia thetopicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT ybarradavide thetopicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT bernabeuezequiel thetopicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT morettonmarcela thetopicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT alvirafernandoc thetopicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT chiappettadiego thetopicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT alonsosilviadelvalle thetopicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT prietomariajimena thetopicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT montanarijorge thetopicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT caliennimarianatalia topicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT mazavegadaniela topicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT tempranacfacundo topicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT izquierdomariacecilia topicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT ybarradavide topicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT bernabeuezequiel topicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT morettonmarcela topicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT alvirafernandoc topicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT chiappettadiego topicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT alonsosilviadelvalle topicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT prietomariajimena topicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo
AT montanarijorge topicalnanodeliveryofvismodegibenhancesitsskinpenetrationandperformanceinvitrowhilereducingitstoxicityinvivo