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).
Highlights
Zeolites that has been a microporous mineral component of aorvolcanic rock from group of natural zeolites has extensively tested as a chelating agent as an adjuvant in the cancer therapy, because of itsthat cation been extensively tested as a chelating agent or as an adjuvant in cancer therapy, because of its cation exchanging and chelating properties [6,7]
N2-sorption analysis was used to assess the porous features of the hosts
Zeolites are used as drug delivery systems for small molecules due to their unique porous characteristics and when the pore size can be matched to the size of drug molecules [35]
Summary
Skin-targeted topical delivery systems are needed to assure sustained release of the drugs and toSkin-targeted topical systems are needed to for assure release of the drugs and maintain a localized effect.deliveryNew drug delivery systems localsustained release of antineoplastic agents to maintain a localized effect.New drug delivery systems for local release of antineoplastic agents represent an alternative strategy to systemic administration, having many advantages such as high representbetter an alternative strategy systemic administration, having many advantages such as high stability, bioavailability, andtoreduced toxic side effects [1,2].stability, better and reduced toxic effects [1,2].Today, bothbioavailability, synthetic and natural zeolites areside increasingly used as drug delivery systems for theirToday, both synthetic and natural zeolites are increasingly used as drug systemsisfor high loading capacity and controlled release of small drug molecules [3,4,5].deliveryClinoptilolite a their high loading capacity and controlled release of small drug moleculesClinoptilolite is microporous mineral component of a volcanic rock from the group of natural [3,4,5].zeolites that has been a microporous mineral component of aorvolcanic rock from group of natural zeolites has extensively tested as a chelating agent as an adjuvant in the cancer therapy, because of itsthat cation been extensively tested as a chelating agent or as an adjuvant in cancer therapy, because of its cation exchanging and chelating properties [6,7]. Skin-targeted topical systems are needed to for assure release of the drugs and maintain a localized effect.delivery. New drug delivery systems for local release of antineoplastic agents represent an alternative strategy to systemic administration, having many advantages such as high representbetter an alternative strategy systemic administration, having many advantages such as high stability, bioavailability, andtoreduced toxic side effects [1,2]. Zeolites that has been a microporous mineral component of aorvolcanic rock from group of natural zeolites has extensively tested as a chelating agent as an adjuvant in the cancer therapy, because of itsthat cation been extensively tested as a chelating agent or as an adjuvant in cancer therapy, because of its cation exchanging and chelating properties [6,7]. Published studies on clinoptilolite confirmed the bimodal porous of properties this material [8,9,10]
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