RESUMO
In the present review we discuss different approaches to pharmaceutical applications of marine lipids. Investigation of the use of marine lipids as dermal permeation enhancers, the synthesis of triacylglycerols highly enriched in polyunsaturated fatty acids, dermal pro-drugs derivatives of unsaturated fatty acids and diacyl glyceryl derivatives, and the possible synthesis of soft disinfectants from marine fatty acids.
Assuntos
Lipídeos/química , Biologia Marinha , Pró-Fármacos , Ácidos Graxos Insaturados/síntese química , Ácidos Graxos Insaturados/química , Absorção CutâneaRESUMO
Diacyl glyceryl ester derivatives of naproxen were synthesized and tested for transdermal and dermal administration. Diacyl derivatives of aliphatic acids of various chain length were compared. The pharmaceutical properties of these compounds, such as lipophilicity, hydrolysis in a buffer solution at various pH values and degradation in human serum and hairless mouse skin homogenate, were investigated. All the diacyl derivatives were relatively stable in a neutral buffer solution, but were rapidly degraded to release naproxen in human serum and hairless mouse skin homogenate. The diacyl compounds could not penetrate hairless mouse skin in vitro. However, significant absorption into the skin could be measured, and this increased with increasing lipophilicity. A more than 100-fold difference in absorption was observed. The prodrugs were slowly hydrolyzed to naproxen inside the skin. The release of naproxen to the receptor compartment of diffusion cells showed that this type of prodrug could be used for controlled drug delivery.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Diglicerídeos/farmacocinética , Naproxeno/farmacocinética , Pró-Fármacos/farmacocinética , Absorção Cutânea , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Soluções Tampão , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Preparações de Ação Retardada , Diglicerídeos/síntese química , Diglicerídeos/química , Feminino , Meia-Vida , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Pelados , Camundongos Endogâmicos C3H , Naproxeno/síntese química , Naproxeno/química , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pele/metabolismoRESUMO
The effects of several marine lipids on the penetration of hydrocortisone and nitroglycerin through excised hairless mouse skin have been studied. Fatty acid extracts obtained by hydrolysis of Portuguese dog-fish-liver-oil or by hydrolysis of cod-liver-oil were shown to be effective skin penetration enhancers. Phospholipid obtained from squid was also shown to be effective enhancer. However, the enhancing effect of the marine products could generally be associated with their content of free unsaturated fatty acids. The fatty acid extract obtained from cod-liver-oil caused insignificant skin irritation when incorporated into an ointment base and applied to human skin.
