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Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization

Background: Capsaicin (CPS) is a highly selective agonist of the transient receptor potential vanilloid type 1 (TRPV1) with a nanomolar affinity. High doses or prolonged exposure to CPS induces TRPV1 defunctionalization and, although this effect is currently used for the treatment of thermal hyperal...

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Autores principales: Puglia, Carmelo, Santonocito, Debora, Bonaccorso, Angela, Musumeci, Teresa, Ruozi, Barbara, Pignatello, Rosario, Carbone, Claudia, Parenti, Carmela, Chiechio, Santina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238012/
https://www.ncbi.nlm.nih.gov/pubmed/32290081
http://dx.doi.org/10.3390/pharmaceutics12040339
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author Puglia, Carmelo
Santonocito, Debora
Bonaccorso, Angela
Musumeci, Teresa
Ruozi, Barbara
Pignatello, Rosario
Carbone, Claudia
Parenti, Carmela
Chiechio, Santina
author_facet Puglia, Carmelo
Santonocito, Debora
Bonaccorso, Angela
Musumeci, Teresa
Ruozi, Barbara
Pignatello, Rosario
Carbone, Claudia
Parenti, Carmela
Chiechio, Santina
author_sort Puglia, Carmelo
collection PubMed
description Background: Capsaicin (CPS) is a highly selective agonist of the transient receptor potential vanilloid type 1 (TRPV1) with a nanomolar affinity. High doses or prolonged exposure to CPS induces TRPV1 defunctionalization and, although this effect is currently used for the treatment of thermal hyperalgesia in chronic pain conditions, it is responsible of detrimental effects, such as denervation of sensory fibers. The aim of the present study was to formulate CPS loaded lipid nanocarriers (CPS-LN) in order to optimize CPS release, thus preventing TRPV1 internalization and degradation. Methods: CPS-LNs were formulated and characterized by in vitro studies. The activation of TRPV1 receptors after CPS-LN administration was evaluated by measuring spontaneous pain that was induced by local injection into the plantar surface of the mouse hind-paw. Moreover, the expression of TRPV1 in the skin was evaluated by western blot analysis in CPS-LN injected mice and then compared to a standard CPS solution (CPS-STD). Results: CPS inclusion in LN induced a lower pain response when compared to CPS-STD; further, it prevented TRPV1 down-regulation in the skin, while CPS-STD induced a significant reduction of TRPV1 expression. Conclusions: Drug encapsulation in lipid nanoparticles produced an optimization of CPS release, thus reducing mice pain behavior and avoiding the effects that are caused by TRPV1 defunctionalization related to a prolonged activation of this receptor.
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spelling pubmed-72380122020-05-28 Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization Puglia, Carmelo Santonocito, Debora Bonaccorso, Angela Musumeci, Teresa Ruozi, Barbara Pignatello, Rosario Carbone, Claudia Parenti, Carmela Chiechio, Santina Pharmaceutics Article Background: Capsaicin (CPS) is a highly selective agonist of the transient receptor potential vanilloid type 1 (TRPV1) with a nanomolar affinity. High doses or prolonged exposure to CPS induces TRPV1 defunctionalization and, although this effect is currently used for the treatment of thermal hyperalgesia in chronic pain conditions, it is responsible of detrimental effects, such as denervation of sensory fibers. The aim of the present study was to formulate CPS loaded lipid nanocarriers (CPS-LN) in order to optimize CPS release, thus preventing TRPV1 internalization and degradation. Methods: CPS-LNs were formulated and characterized by in vitro studies. The activation of TRPV1 receptors after CPS-LN administration was evaluated by measuring spontaneous pain that was induced by local injection into the plantar surface of the mouse hind-paw. Moreover, the expression of TRPV1 in the skin was evaluated by western blot analysis in CPS-LN injected mice and then compared to a standard CPS solution (CPS-STD). Results: CPS inclusion in LN induced a lower pain response when compared to CPS-STD; further, it prevented TRPV1 down-regulation in the skin, while CPS-STD induced a significant reduction of TRPV1 expression. Conclusions: Drug encapsulation in lipid nanoparticles produced an optimization of CPS release, thus reducing mice pain behavior and avoiding the effects that are caused by TRPV1 defunctionalization related to a prolonged activation of this receptor. MDPI 2020-04-10 /pmc/articles/PMC7238012/ /pubmed/32290081 http://dx.doi.org/10.3390/pharmaceutics12040339 Text en © 2020 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
Puglia, Carmelo
Santonocito, Debora
Bonaccorso, Angela
Musumeci, Teresa
Ruozi, Barbara
Pignatello, Rosario
Carbone, Claudia
Parenti, Carmela
Chiechio, Santina
Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization
title Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization
title_full Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization
title_fullStr Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization
title_full_unstemmed Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization
title_short Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization
title_sort lipid nanoparticle inclusion prevents capsaicin-induced trpv1 defunctionalization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238012/
https://www.ncbi.nlm.nih.gov/pubmed/32290081
http://dx.doi.org/10.3390/pharmaceutics12040339
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