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Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice

Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU)-loaded clinoptilolite-based delivery system. Two clinoptilolite ionic forms—hydrogen form (HCLI) and sodium form (NaCLI)—were prepared, allowing a loading degree of about 5–6 mg BCNU/g of zeolite matrix due to th...

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Autores principales: Ghiciuc, Cristina Mihaela, Strat, Aurel Lulu, Ochiuz, Lacramioara, Lupusoru, Catalina Elena, Ignat, Maria, Vasile, Aurelia, Grigorovici, Alexandru, Stoleriu, Iulian, Solcan, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150160/
https://www.ncbi.nlm.nih.gov/pubmed/29156646
http://dx.doi.org/10.3390/molecules22112014
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author Ghiciuc, Cristina Mihaela
Strat, Aurel Lulu
Ochiuz, Lacramioara
Lupusoru, Catalina Elena
Ignat, Maria
Vasile, Aurelia
Grigorovici, Alexandru
Stoleriu, Iulian
Solcan, Carmen
author_facet Ghiciuc, Cristina Mihaela
Strat, Aurel Lulu
Ochiuz, Lacramioara
Lupusoru, Catalina Elena
Ignat, Maria
Vasile, Aurelia
Grigorovici, Alexandru
Stoleriu, Iulian
Solcan, Carmen
author_sort Ghiciuc, Cristina Mihaela
collection PubMed
description Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU)-loaded clinoptilolite-based delivery system. Two clinoptilolite ionic forms—hydrogen form (HCLI) and sodium form (NaCLI)—were prepared, allowing a loading degree of about 5–6 mg BCNU/g of zeolite matrix due to the dual porous feature of clinoptilolite. Clinoptilolite-based delivery systems released 35.23% of the load in 12 h for the BCNU@HCLI system and only 10.82% for the BCNU@NaCLI system. The BCNU@HCLI system was chosen to develop gel and cream semisolid dosage forms. The cream (C_BCNU@HCLI) released 29.6% of the loaded BCNU after 12 h in the Nylon synthetic membrane test and 31.6% in the collagen membrane test, higher by comparison to the gel. The new cream was evaluated in vivo in a chemically induced model of skin cancer in mice. Quantitative immunohistochemistry analysis showed stronger inhibition of B-cell lymphoma-2 (bcl-2) and cyclooxygenase 2 (cox-2) protein expression, known markers for cancer survival and aggressiveness, after the treatment with C_BCNU@HCLI by comparison to all the control treatment types, including an off-label magistral formula commercially available Carmustine cream as reference, bringing evidence that a clinoptilolite-based delivery systems could be used as a cancer drug carriers and controlled release systems (skin-targeted topical delivery systems).
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spelling pubmed-61501602018-11-13 Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice Ghiciuc, Cristina Mihaela Strat, Aurel Lulu Ochiuz, Lacramioara Lupusoru, Catalina Elena Ignat, Maria Vasile, Aurelia Grigorovici, Alexandru Stoleriu, Iulian Solcan, Carmen Molecules Article Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU)-loaded clinoptilolite-based delivery system. Two clinoptilolite ionic forms—hydrogen form (HCLI) and sodium form (NaCLI)—were prepared, allowing a loading degree of about 5–6 mg BCNU/g of zeolite matrix due to the dual porous feature of clinoptilolite. Clinoptilolite-based delivery systems released 35.23% of the load in 12 h for the BCNU@HCLI system and only 10.82% for the BCNU@NaCLI system. The BCNU@HCLI system was chosen to develop gel and cream semisolid dosage forms. The cream (C_BCNU@HCLI) released 29.6% of the loaded BCNU after 12 h in the Nylon synthetic membrane test and 31.6% in the collagen membrane test, higher by comparison to the gel. The new cream was evaluated in vivo in a chemically induced model of skin cancer in mice. Quantitative immunohistochemistry analysis showed stronger inhibition of B-cell lymphoma-2 (bcl-2) and cyclooxygenase 2 (cox-2) protein expression, known markers for cancer survival and aggressiveness, after the treatment with C_BCNU@HCLI by comparison to all the control treatment types, including an off-label magistral formula commercially available Carmustine cream as reference, bringing evidence that a clinoptilolite-based delivery systems could be used as a cancer drug carriers and controlled release systems (skin-targeted topical delivery systems). MDPI 2017-11-20 /pmc/articles/PMC6150160/ /pubmed/29156646 http://dx.doi.org/10.3390/molecules22112014 Text en © 2017 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
Ghiciuc, Cristina Mihaela
Strat, Aurel Lulu
Ochiuz, Lacramioara
Lupusoru, Catalina Elena
Ignat, Maria
Vasile, Aurelia
Grigorovici, Alexandru
Stoleriu, Iulian
Solcan, Carmen
Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice
title Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice
title_full Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice
title_fullStr Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice
title_full_unstemmed Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice
title_short Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice
title_sort inhibition of bcl-2 and cox-2 protein expression after local application of a new carmustine-loaded clinoptilolite-based delivery system in a chemically induced skin cancer model in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150160/
https://www.ncbi.nlm.nih.gov/pubmed/29156646
http://dx.doi.org/10.3390/molecules22112014
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