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
Cristina Mihaela Ghiciuc,
Aurel Lulu Strat,
Lacramioara Ochiuz,
Catalina Elena Lupusoru,
Maria Ignat,
Aurelia Vasile,
Alexandru Grigorovici,
Iulian Stoleriu,
Carmen Solcan
Affiliations
Cristina Mihaela Ghiciuc
Department of Pharmacology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16, University Street, 700115 Iasi, Romania
Aurel Lulu Strat
Department of Pharmacology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16, University Street, 700115 Iasi, Romania
Lacramioara Ochiuz
Department of Pharmaceutical Technology, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, 16, University Street, 700115 Iasi, Romania
Catalina Elena Lupusoru
Department of Pharmacology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16, University Street, 700115 Iasi, Romania
Maria Ignat
Faculty of Chemistry, “Al. I. Cuza” University, 11, Blvd. Carol the 1st, 700560 Iasi, Romania
Aurelia Vasile
Faculty of Chemistry, “Al. I. Cuza” University, 11, Blvd. Carol the 1st, 700560 Iasi, Romania
Alexandru Grigorovici
Department of Surgery, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16, University Street, 700115 Iasi, Romania
Iulian Stoleriu
Faculty of Mathematics, “Al. I. Cuza” University, 11, Blvd. Carol the 1st, 700506 Iasi, Romania
Carmen Solcan
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
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).
