Cargando…

Use of Pluronic Surfactants in Gel Formulations of Photosensitive 1,4-Dihydropyridine Derivatives: A Potential Approach in the Treatment of Neuropathic Pain

1,4-Dihydropyridines (DHPs) are the most important class of L-type calcium channel blockers that are employed for the treatment of cardiovascular diseases, particularly hypertension. Various modifications on this scaffold lead to the discovery of new DHPs blocking different types of calcium channels...

Descripción completa

Detalles Bibliográficos
Autores principales: Ioele, Giuseppina, Muzzalupo, Rita, Gündüz, Miyase Gözde, De Luca, Michele, Mazzotta, Elisabetta, Grande, Fedora, Occhiuzzi, Maria Antonietta, Garofalo, Antonio, Ragno, Gaetano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070562/
https://www.ncbi.nlm.nih.gov/pubmed/33920090
http://dx.doi.org/10.3390/pharmaceutics13040527
_version_ 1783683499135336448
author Ioele, Giuseppina
Muzzalupo, Rita
Gündüz, Miyase Gözde
De Luca, Michele
Mazzotta, Elisabetta
Grande, Fedora
Occhiuzzi, Maria Antonietta
Garofalo, Antonio
Ragno, Gaetano
author_facet Ioele, Giuseppina
Muzzalupo, Rita
Gündüz, Miyase Gözde
De Luca, Michele
Mazzotta, Elisabetta
Grande, Fedora
Occhiuzzi, Maria Antonietta
Garofalo, Antonio
Ragno, Gaetano
author_sort Ioele, Giuseppina
collection PubMed
description 1,4-Dihydropyridines (DHPs) are the most important class of L-type calcium channel blockers that are employed for the treatment of cardiovascular diseases, particularly hypertension. Various modifications on this scaffold lead to the discovery of new DHPs blocking different types of calcium channels. Among them, the T-type calcium channel has recently attracted great interest due to its role in chronic pain conditions. In this study, we selected three newly synthesized DHPs (HM8, HM10 and MD20) with different selectivity profiles to the T-type calcium channel and formulated them in micellar solutions and micellar-in-gel matrices to be tested for potential topical use in the treatment of neuropathic pain. To prevent the well-known sensitivity to light of the DHPs, the studied compounds were entrapped in colloidal aggregates obtained by using edible Pluronic(®) surfactants and adding α-tocopherol as an antioxidant. All the prepared formulations were exposed to stressing light, according to international rules. Along with the degradation experiments, the concentrations of the parent compounds and by-products were calculated by multivariate curve resolution—alternating least squares (MCR-ALS) applied to the spectral data. The defined formulations proved suitable as light-stable matrices for the DHP compounds, showing an increase in stability for HM8 and MD20 and an almost complete photoprotection for HM10, compared to ethanol solutions and standard gel formulations.
format Online
Article
Text
id pubmed-8070562
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-80705622021-04-26 Use of Pluronic Surfactants in Gel Formulations of Photosensitive 1,4-Dihydropyridine Derivatives: A Potential Approach in the Treatment of Neuropathic Pain Ioele, Giuseppina Muzzalupo, Rita Gündüz, Miyase Gözde De Luca, Michele Mazzotta, Elisabetta Grande, Fedora Occhiuzzi, Maria Antonietta Garofalo, Antonio Ragno, Gaetano Pharmaceutics Article 1,4-Dihydropyridines (DHPs) are the most important class of L-type calcium channel blockers that are employed for the treatment of cardiovascular diseases, particularly hypertension. Various modifications on this scaffold lead to the discovery of new DHPs blocking different types of calcium channels. Among them, the T-type calcium channel has recently attracted great interest due to its role in chronic pain conditions. In this study, we selected three newly synthesized DHPs (HM8, HM10 and MD20) with different selectivity profiles to the T-type calcium channel and formulated them in micellar solutions and micellar-in-gel matrices to be tested for potential topical use in the treatment of neuropathic pain. To prevent the well-known sensitivity to light of the DHPs, the studied compounds were entrapped in colloidal aggregates obtained by using edible Pluronic(®) surfactants and adding α-tocopherol as an antioxidant. All the prepared formulations were exposed to stressing light, according to international rules. Along with the degradation experiments, the concentrations of the parent compounds and by-products were calculated by multivariate curve resolution—alternating least squares (MCR-ALS) applied to the spectral data. The defined formulations proved suitable as light-stable matrices for the DHP compounds, showing an increase in stability for HM8 and MD20 and an almost complete photoprotection for HM10, compared to ethanol solutions and standard gel formulations. MDPI 2021-04-10 /pmc/articles/PMC8070562/ /pubmed/33920090 http://dx.doi.org/10.3390/pharmaceutics13040527 Text en © 2021 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
Ioele, Giuseppina
Muzzalupo, Rita
Gündüz, Miyase Gözde
De Luca, Michele
Mazzotta, Elisabetta
Grande, Fedora
Occhiuzzi, Maria Antonietta
Garofalo, Antonio
Ragno, Gaetano
Use of Pluronic Surfactants in Gel Formulations of Photosensitive 1,4-Dihydropyridine Derivatives: A Potential Approach in the Treatment of Neuropathic Pain
title Use of Pluronic Surfactants in Gel Formulations of Photosensitive 1,4-Dihydropyridine Derivatives: A Potential Approach in the Treatment of Neuropathic Pain
title_full Use of Pluronic Surfactants in Gel Formulations of Photosensitive 1,4-Dihydropyridine Derivatives: A Potential Approach in the Treatment of Neuropathic Pain
title_fullStr Use of Pluronic Surfactants in Gel Formulations of Photosensitive 1,4-Dihydropyridine Derivatives: A Potential Approach in the Treatment of Neuropathic Pain
title_full_unstemmed Use of Pluronic Surfactants in Gel Formulations of Photosensitive 1,4-Dihydropyridine Derivatives: A Potential Approach in the Treatment of Neuropathic Pain
title_short Use of Pluronic Surfactants in Gel Formulations of Photosensitive 1,4-Dihydropyridine Derivatives: A Potential Approach in the Treatment of Neuropathic Pain
title_sort use of pluronic surfactants in gel formulations of photosensitive 1,4-dihydropyridine derivatives: a potential approach in the treatment of neuropathic pain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070562/
https://www.ncbi.nlm.nih.gov/pubmed/33920090
http://dx.doi.org/10.3390/pharmaceutics13040527
work_keys_str_mv AT ioelegiuseppina useofpluronicsurfactantsingelformulationsofphotosensitive14dihydropyridinederivativesapotentialapproachinthetreatmentofneuropathicpain
AT muzzaluporita useofpluronicsurfactantsingelformulationsofphotosensitive14dihydropyridinederivativesapotentialapproachinthetreatmentofneuropathicpain
AT gunduzmiyasegozde useofpluronicsurfactantsingelformulationsofphotosensitive14dihydropyridinederivativesapotentialapproachinthetreatmentofneuropathicpain
AT delucamichele useofpluronicsurfactantsingelformulationsofphotosensitive14dihydropyridinederivativesapotentialapproachinthetreatmentofneuropathicpain
AT mazzottaelisabetta useofpluronicsurfactantsingelformulationsofphotosensitive14dihydropyridinederivativesapotentialapproachinthetreatmentofneuropathicpain
AT grandefedora useofpluronicsurfactantsingelformulationsofphotosensitive14dihydropyridinederivativesapotentialapproachinthetreatmentofneuropathicpain
AT occhiuzzimariaantonietta useofpluronicsurfactantsingelformulationsofphotosensitive14dihydropyridinederivativesapotentialapproachinthetreatmentofneuropathicpain
AT garofaloantonio useofpluronicsurfactantsingelformulationsofphotosensitive14dihydropyridinederivativesapotentialapproachinthetreatmentofneuropathicpain
AT ragnogaetano useofpluronicsurfactantsingelformulationsofphotosensitive14dihydropyridinederivativesapotentialapproachinthetreatmentofneuropathicpain