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Molecules 2017, 22(11), 2014; doi:10.3390/molecules22112014

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

1
Department of Pharmacology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16, University Street, 700115 Iasi, Romania
2
Laboratory of Microbiology, Hospital of Infectious Diseases “Saint Parascheva”, 2, Octav Botez Street, 700116 Iasi, Romania
3
Department of Pharmaceutical Technology, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, 16, University Street, 700115 Iasi, Romania
4
Faculty of Chemistry, “Al. I. Cuza” University, 11, Blvd. Carol the 1st, 700560 Iasi, Romania
5
Department of Surgery, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16, University Street, 700115 Iasi, Romania
6
Faculty of Mathematics, “Al. I. Cuza” University, 11, Blvd. Carol the 1st, 700506 Iasi, Romania
7
Department of Molecular Biology, Histology and Embriology, Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine “Ion Ionescu de la Brad”, 8, Mihail Sadoveanu Alley, 700489 Iasi, Romania
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 27 September 2017 / Revised: 19 November 2017 / Accepted: 6 November 2017 / Published: 20 November 2017
(This article belongs to the Section Medicinal Chemistry)
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Abstract

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). View Full-Text
Keywords: clinoptilolite; zeolite; drug delivery system; skin cream; Carmustine; chemically induced skin cancer; mouse cancer model; cyclooxygenase 2 (cox-2) protein; B-cell lymphoma-2 (bcl-2) protein; quantitative immunohistochemistry; computer aided diagnostic software clinoptilolite; zeolite; drug delivery system; skin cream; Carmustine; chemically induced skin cancer; mouse cancer model; cyclooxygenase 2 (cox-2) protein; B-cell lymphoma-2 (bcl-2) protein; quantitative immunohistochemistry; computer aided diagnostic software
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Ghiciuc, C.M.; Strat, A.L.; Ochiuz, L.; Lupusoru, C.E.; Ignat, M.; Vasile, A.; Grigorovici, A.; Stoleriu, I.; Solcan, C. 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. Molecules 2017, 22, 2014.

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