RESUMO
2-n-propylquinoline is presently a drug-candidate for the treatment of visceral leishmaniosis in pre-clinical development. As this compound is in an oily state, it needs to be formulated and the objectives of this study are: to prepare a formulation; to demonstrate that the new salted formulation did not alter the activity of the active ingredient; and finally, that this activity was quite good compared to the reference oral drug, miltefosine. Therefore, a 2-n-propylquinoline formulation, as camphorsulfonic salt, was prepared and characterised. On the Leishmania donovani / Balb/c mice model, a treatment by oral route at 60 mmoles/kg/day for ten consecutive days with this formulation was compared to 2-n-propylquinoline alone and to miltefosine, the oral reference drug. The salt formulation did not alter the activity of the 2-n-propylquinoline. The formulation reduced the parasite burden of 76% compared to 89% for miltefosine (not significant). The characteristics of this formulation results in a suitable drugability of 2-n-propylquinoline for further studies.
Assuntos
Antiprotozoários/farmacologia , Leishmania donovani/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Quinolinas/farmacologia , Administração Oral , Animais , Antiprotozoários/administração & dosagem , Antiprotozoários/química , Química Farmacêutica , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos BALB C , Fosforilcolina/administração & dosagem , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacologia , Quinolinas/administração & dosagem , Quinolinas/químicaRESUMO
Noticeable modifications of in-serum transfection efficiency of dioctadecylamidoglycyl-spermine (DOGS)-DNA complexes are observed, depending on DNA condensation conditions. The structures of the complexes are studied, keeping in mind the variability of lipid polymorphism, by cryo-transmission electron microscopy and X-ray diffraction. By increasing both pH and ionic strength, well-organised lamellar structures with a period of 65 A replace supramicellar aggregates. A relationship between the structures and their in-vitro transfection activity is established. Efficiency in the presence of serum is maintained when a lamellar arrangement is involved.