RESUMO
PURPOSE: Acyclic nucleoside phosphonates possess unique antiviral and antineoplastic activities; however, their polar phosphonate moiety is associated with low ability to cross biological membranes. We explored the potential of transdermal and topical delivery of 2,6-diaminopurine derivative cPr-PMEDAP. METHODS: In vitro diffusion of cPr-PMEDAP was investigated using formulations at different pH and concentration and with permeation enhancer through porcine and human skin. RESULTS: Ability of 0.1-5% cPr-PMEDAP to cross human skin barrier was very low with flux values ~40 ng/cm(2)/h, the majority of compound found in the stratum corneum. The highest permeation rates were found at pH 6; increased donor concentration had no influence. The permeation enhancer dodecyl 6-dimethylaminohexanoate (DDAK, 1%) increased flux of cPr-PMEDAP (up to 61 times) and its concentration in nucleated epidermis (up to ~0.5 mg of cPr-PMEDAP/g of the tissue). No deamination of cPr-PMEDAP into PMEG occurred during permeation studies, but N-dealkylation into PMEDAP mediated by skin microflora was observed. CONCLUSIONS: Transdermal or topical application of cPr-PMEDAP enabled by the permeation enhancer DDAK may provide an attractive alternative route of administration of this potent antitumor and antiviral compound.
Assuntos
Antineoplásicos/administração & dosagem , Antivirais/administração & dosagem , Caproatos/metabolismo , Metilaminas/metabolismo , Organofosfonatos/administração & dosagem , Pele/metabolismo , Adenina/administração & dosagem , Administração Cutânea , Animais , Dimetilaminas , Dodecanol , Humanos , Concentração de Íons de Hidrogênio , Permeabilidade , SuínosRESUMO
Topical skin lipid supplementation may provide opportunities for controlling ceramide (Cer) deficiency in skin diseases such as atopic dermatitis or psoriasis. Here we describe the synthesis of a long-chain 7-nitrobenzo[c][1,2,5]oxadiazol-4-yl (NBD)-labeled Cer and its different penetration through human skin compared to widely used short-chain fluorescent Cer tools.
Assuntos
4-Cloro-7-nitrobenzofurazano/metabolismo , Ceramidas/metabolismo , Corantes Fluorescentes/metabolismo , Pele/metabolismo , 4-Cloro-7-nitrobenzofurazano/síntese química , Bisbenzimidazol/metabolismo , Ceramidas/síntese química , Dermatite Atópica/metabolismo , Fluorescência , Corantes Fluorescentes/síntese química , Humanos , Permeabilidade , Psoríase/metabolismoAssuntos
Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Neoplasias do Apêndice/complicações , Neoplasias do Apêndice/diagnóstico , Apendicite/complicações , Apendicite/diagnóstico , Divertículo Ileal/complicações , Divertículo Ileal/diagnóstico , Adulto , Apendicite/cirurgia , Humanos , MasculinoRESUMO
Stomach volvulus in its acute form is a serious sudden disorder in the abdominal cavity. The case of stomach volvulus, that had been successfully surgically solved, is described in the presented paper. Even though the volvulus was not caused by the hiatus hernia, the antireflux fundoplication according to Nissen-Rossetti was performed besides the frontal gastropexy.