Fases lamelares associadas a lipídeos fisiológicos e metotrexato para tratamento tópico da psoríase

Abstract

Psoriasis, a disease characterized by deficient epidermal differentiation, is usually treated with methotrexate, an effective drug, but associated with severe systemic toxicity. Although topical administration is an alternative, it often proves to be inefficient because of its limited cutaneous penetration. Liquid crystals are presented as an appropriate vehicle because when organized similarly to the corneal lipid matrix they may increase cutaneous penetration of drugs and cutaneous hydration. These results are even more promising when physiological lipids are used, which may facilitate repair of the impaired skin barrier.The objective of this work was to develop lamellar phases containing physiological lipids and methotrexate for potential topical treatment of psoriasis. The behavior of phases was investigated by the construction of ternary phase diagrams and combinations combining different surfactants: polyoxyethylene 2- cetyl ether (OLETH-2), polyoxyethylene 10-cetyl ether (CETETH-10), 20-ethoxylated and 5-propoxylated cetyl alcohol (PPG-5-CETETH-20) or ethylenediamine tetrakis (ethoxylated propoxylated) tetrol (T 701), diethyleneglycol monoethyl ether, as cosurfactant (CoS), stearic acid (SA), oleic acid (OA), cholesterol (CHO) and ceramide 3 (CER), such as physiological lipids and water. Samples were characterized by polarized light microscopy, texture analysis, bioadhesion, rheology and promoting effect through in vitro cutaneous penetration studies. With an extensive study of phase behavior combining a large number of proportions between surfactants, cosurfactant, oily phases and water it was possible to obtain lamellar phases lamellar phases containing CHO, CER, CHO and CER or CoS. It was possible to incorporate 1% methotrexate in all the lamellar phases, which had pH compatible with the cutaneous route. The texture profile assay revealed that the lamellar phases were compressible, adhesive and cohesive, therefore suitable for application to the skin. The bioadhesion work values of the lamellar phases, in general, were higher than those of carbopol gels, traditionally bioadhesive. The oscillatory rheological analysis confirmed the elastic behavior, characteristic of gel, for all the lamellar phases. The evaluation of the promoter effect of liquid crystals showed that C4CHOCER was more efficient in promoting cutaneous retention of hydrophilic substances compared to conventional emulsion with the same components or C4CHO lamellar mesophase, which did not have CER. Therefore, the development of proposed lamellar phases have the potential to become vehicles to increase cutaneous retention of hydrophilic substances such as methotrexate. Besides that, the vehicle itself may prove to be an excellent form of treatment for cutaneous disorders related to dryness, dehydration and abnormal keratinization of the stratum corneum, such as psoriasis, by the presence of physiological lipids.