In vitro skin penetration of a sunscreen cyclodextrin complex loaded in lipospheres

Abstract: Lipospheres loaded with butyl-methoxydibenzoylmethane (BMDBM) or BMDBM complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD) were designed in order to investigate the effect of the complexation on the sunscreen skin absorption. By means of an in vitro technique, cyclodextrin complex provided a significant reduction in sunscreen penetration out of an O/W emulsion whereas no effect was noticed by introducing the complex in a petrolatum jelly formulation. Introduction: The lipophilic nature of most organic sunscreens induces suncare formulation designer to guarantee UV filter accumulation at the skin surface or in the uppermost part of the stratum corneum so preventing its permeation through the skin and the possible subsequent toxic effect and failure in sun protection. For this purpose, microencapsulation in lipospheres was adopted as a strategy to maintain butyl-methoxydibenzoylmethane (BMDBM), an authorized highly efficient UV-A absorber, at the skin surface as well to increase its photostability. Lipospheres, consisting of a solid fat core stabilized by a layer of phospholipid molecules at the surface, were previously developed and evaluated for BMDBM photostability which was found enhanced by the lipid carrier (1). Moreover, complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD) decreased the degree of decomposition and free radical formation upon exposure to simulated sunlight but no effect on filter accumulation in the epidermis was observed (2). Consequently, the present study attempts to entrap BMDBM/HP-β-CD complex in lipospheres in order to evaluate the effect of the microencapsulation on BMDBM percutaneous absorption. The study of percutaneous absorption was carried out by using a lipophilized membrane in a diffusion chamber, on lipospheres containing BMDBM/HP-β-CD complex incorporated in two different vehicles and compared with lipospheres containing BMDBM alone. Experimental methods: Sunscreen-loaded lipospheres were prepared by emulsifying melted tristearin (Fluka Chemie, Buchs, Switzerland) containing BMDBM (Merck, Darmastd, Germany) or BMDBM/HP-β-CD (Aldrich Chimica, Milan, Italy) complex in a 3:1 or 3:3 ratio, respectively, with 2% hydrogenated soybean phosphatidyl-choline (Fluka Chemie) pH 7.4 buffer solution, as described previously (1). Lipospheres were analysed for morphology and size by Scanning Electron Microscopy (SEM) and optical videomicroscopy coupled with epifluorescence, physical state by Differential Scanning Calorimeter (DSC), BMDBM loading level and in vitro release. For the in vitro percutaneous absorption assay, a cellulose acetate membrane (12.56 cm2 surface area) soaked in dodecil alcohol was put in a diffusion chamber connected with 100 ml of ethanol 96%/Mygliol 812 (Sasol Germany GmbH, Witten, Germany) in a ratio of 9:1 as receptor phase, providing sink conditions, kept at 37°C. A portion (300 mg) of petrolatum yelly or an O/W emulsion – water, stearic acid, spermaceti, triethanolamine, glycerine – containing BMDBM or BMDBM/HP-β-CD complex, both in amounts corresponding to 2% of BMDBM, was applied, as donor compartment, on the membrane. At fixed time intervals, 2 ml aliquots of acceptor medium were collected and BMDBM concentration was determined by UV spectrophotometry at a wavelenght of 355 nm. Results and discussion: The loaded lipospheres showed spherical shape and a smooth surface in the presence of BMDBM alone (see Fig. 1a), more irregular shape and wrinkled surface in the presence of BMDBM/HP-β-CD complex (see Fig. 1b). The size was between 10 and 70 m, with the most population in the range of 10-40 m, for both the samples.