Protective effects of a cream containing Dead Sea minerals against UVB-induced stress in human skin.

BACKGROUND: Dead Sea (DS) mud and water are known for their unique composition of minerals, and for their therapeutic properties on psoriasis and other inflammatory skin diseases. Their mode of action, however, remains poorly known. OBJECTIVES: To analyse the ability of Dermud, a leave-on skin preparation containing DS mud and other ingredients like DS water, zinc oxide, aloe-vera extract, pro-vitamin B5 and vitamin E, to antagonize biological effects induced by UVB irradiation in skin when topically applied in organ cultures. METHODS: We have used human skin organ cultures as a model to assess the biological effects of UVB irradiation and of Dermud cream topical application. Skin pieces were analysed for mitochondrial activity by MTT assay, for apoptosis by caspase 3 assay, for cytokine secretion by solid phase ELISA, for overall antioxidant capacity by ferric reducing antioxidant power and Oxygen radical absorbance capacity assays (epidermis) or by cyclic voltammetry (external medium), and for uric acid (UA) content by HPLC. RESULTS: We report that UVB irradiation decreases cell viability, total antioxidant capacity and UA contents in the epidermis of skin organ cultures, while increasing the levels of apoptosis in cells and their cytokine secretion. Topical application of Dermud decreased all these effects significantly. CONCLUSIONS: Our results clearly show that Dermud has protective, anti-oxidant and anti-inflammatory properties that can antagonize biological effects of UVB irradiation in skin. It may therefore be able to reduce skin photodamage and photoaging, and more generally to reduce oxidative stress and inflammation in skin pathologies.

Luminal delivery and dosing considerations of local celecoxib administration to colorectal cancer.

The purpose of this study was to develop a biodegradable drug platform composed of chitosan and guar gum and to explore the possibility of using it for local adjuvant or neoadjuvant therapy of colorectal cancer. Celecoxib (Cx), a chemopreventative drug for familial adenomatous polyposis (FAP) and under trial for reducing post surgical colorectal malignancies, was selected as a model drug for this topical system because of the contraindications that are associated with its systemic administration. Films made of chitosan (Ct) and guar gum (GG) were prepared, characterized for equilibrium swelling, mucoadhesion, in vitro and in vivo degradation and loaded with Cx. Short term dosing studies in vitro were performed in the HT-29 colon carcinoma cell line that was incubated with Cx using the MTT test to assess IC50. The impact of a single high dose was evaluated and compared with a repeating low-dose regimen. In vivo dosing experiments with Cx were performed in the perfused intestine of the anaesthetized rat. Measuring tissue LDH assessed epithelium injury. Mechanical, mucoadhesion and in vitro degradation of the polysaccharide films were dictated by manipulating the ratios of Ct and GG. The addition of rat cecal contents to the dissolution medium increased the total Cx released from those films containing high amounts of GG. MTT reduction, a measure of cell proliferation, diminished as a function of increasing drug concentration and exposure time in the HT-29 cell line studies. Local high concentrations of Cx were shown to impede the proliferation of cancer cells directly, while chemoprevention has been demonstrated with low Cx doses. Healthy cells were shown to be sensitive to high Cx doses. Maximum therapeutic efficiency in the context of minimal healthy tissue exposure would thus be predicted utilizing a local delivery system such as the proposed adhesive, biodegradable polysaccharide composites.