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

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).

The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval

“…These results highlighted the role of DMBA as an initiator, as well as the importance of the combination of these two agents [274]. Regarding the screening of new drug candidates, several compounds have been evaluated using this combined model (DMBA/TPA) to induce skin cancer, such as the natural compound withaferin A [275] and clinoptilolitebased delivery system loading carmustine [276].…”

Gel Formulations for Topical Treatment of Skin Cancer: A Review

“…The nanostructures obtained were further chemically cross-linked using citric acid under mild conditions. The predecessor of mesoporous silica-inorganic zeolites-have been used as a skin delivery system for carmustine after their inclusion in the HPC gel [169].…”