Skin delivery potency and antitumor activities of temozolomide ester prodrugs

Clinical trials have shown temozolomide to be an effective agent for treatment of malignant melanoma. In order to investigate its suitability for delivery via the skin, a series of temozolomide esters was synthesized as prodrugs. In vitro assays demonstrated temozolomide, temozolomide acid and the hexyl ester equi-effective against selected cancer cell lines. The susceptibility of the esters to enzyme hydrolysis and their effectiveness for application to the skin were investigated. The esters effectively diffuse through rat skin and the hexyl ester demonstrated profound potency for penetrating through skin. Topical application of 5% (w/v) hexyl ester in DMSO solution on a mouse model demonstrated a significant inhibition of tumor growth. These results suggest that temozolomide esters could be an effective alternative to temozolomide in the treatment of skin cancer. © 2005 Elsevier Ireland Ltd. All rights reserved.

Mechanisms of drying of particulate slurries

The literature on the evaporation of pure liquid drops and the drying of drops of solutions and slurries has been reviewed with particular reference to spray drying. A 0.1-0.2 mm glass filament-thermocouple was constructed and used to study simultaneously, heat and mass transfer from a single suspended drop placed in a humidity and temperature controlled, 28 mm OD vertical wind tunnel. Heat conduction through the filament was minimised eg at 100¦C it accounted for only 9.3% of the total heat transferred to a drop. Evaporation of single water drops was also studied in a 101 mm OD vertical wind tunnel. The Nusselt number was found to be a function of the Reynolds, Prandtl and Transfer number over an air temperature range of 17¦C to 107¦C. The proposed correlation is: Nu = 2+(-12.96B+0.76)Re¦-5Pr0-33 Experimental drying studies were carried out on single suspended 1 to 2.5 mm diameter drops of aqueous sodium sulphate decahydrate, sodium chloride, potassium sulphate, copper sulphate and sodium acetate solutions and slurries at temperatures of 20¦C to 124¦C. Dried crusts were examined by Scanning Electron Microscopy. The drying history of any material depended upon the nature of the crust formed. Sodium acetate formed a non-rigid skin prior to the formation of a rigid crust. A modified receding evaporation interface model was proposed for the drying of solutions and slurries. This covered both the constant rate period prior to crust formation and the subsequent falling rate period. The model was solved numerically for the variation in core temperature, drop weight and crust thickness. Good agreement was obtained between model predictions and experimental results for materials forming rigid crusts i.e. sodium sulphate decahydrate, sodium chloride, potassium sulphate and copper sulphate. However, the drying histories of drops of 10-20% weight initial concentration sodium acetate were unpredictable since formation of a non-rigid skin deviated from the model assumption of a rigid outer surface. At higher initial concentrations (40% weight) where a rigid crust was formed for sodium acetate, good agreement was obtained between experimental results and model predictions. Single suspended drop studies are concluded to provide a valuable insight into the drying mechanisms of specific solutions and slurries.

Towards standardization of UV eye protection:what can be learned from photodermatology?

While knowledge about standardization of skin protection against ultraviolet radiation (UVR) has progressed over the past few decades, there is no uniform and generally accepted standardized measurement for UV eye protection. The literature provides solid evidence that UV can induce considerable damage to structures of the eye. As well as damaging the eyelids and periorbital skin, chronic UV exposure may also affect the conjunctiva and lens. Clinically, this damage can manifest as skin cancer and premature skin ageing as well as the development of pterygia and premature cortical cataracts. Modern eye protection, used daily, offers the opportunity to prevent these adverse sequelae of lifelong UV exposure. A standardized, reliable and comprehensive label for consumers and professionals is currently lacking. In this review we (i) summarize the existing literature about UV radiation-induced damage to the eye and surrounding skin; (ii) review the recent technological advances in UV protection by means of lenses; (iii) review the definition of the Eye-Sun Protection Factor (E-SPF®), which describes the intrinsic UV protection properties of lenses and lens coating materials based on their capacity to absorb or reflect UV radiation; and (iv) propose a strategy for establishing the biological relevance of the E-SPF. © 2013 John Wiley & Sons A/S.