RESUMO
This work is devoted to the study and obtaining of new radioprotective agents based on natural flavonoid genistein and spherical amorphous nanoparticles (SANPs) produced from a mixture of birch bark triterpenoids. The physicochemical characteristics of the nanoparticles were studied by electron microscopy, dynamic light scattering, and UV-VIS spectroscopy. The radioprotective efficacy of the nanodrug in vivo and the possibility of its use as a radioprotective agent was shown.
Assuntos
Betula , Genisteína/farmacologia , Nanopartículas Metálicas , Fitoterapia , Preparações de Plantas/farmacologia , Protetores contra Radiação/farmacologia , Animais , Animais não Endogâmicos , Betula/química , Ésteres do Colesterol/química , Avaliação Pré-Clínica de Medicamentos , Genisteína/síntese química , Genisteína/química , Genisteína/toxicidade , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Camundongos , Tamanho da Partícula , Triterpenos Pentacíclicos/química , Casca de Planta/química , Preparações de Plantas/síntese química , Preparações de Plantas/química , Preparações de Plantas/toxicidade , Lesões Experimentais por Radiação/tratamento farmacológico , Protetores contra Radiação/síntese química , Protetores contra Radiação/química , Protetores contra Radiação/toxicidade , Distribuição Aleatória , Análise de Sobrevida , Resultado do Tratamento , Triterpenos/químicaRESUMO
We have used an original chromatography/mass spectrometry technique to study the pharmacokinetics of dipeptide carnosine in C57 Black/6 mice after intra-peritoneal administration of the drug at a dose of 1 g/kg. The basic pharmacokinetic characteristics of carnosine were measured the in the blood and brain. The obtained concentration-time curve has a biexponential character. It is shown that the maximum concentration of carnosine in the blood plasma is Cmax = 1081.75 ± 124.24 µg/mL and it is achieved in a time interval of Tmax = 0.25 h. We showed that i.p. administration of exogenous carnosine could significantly increase the concentration of that substance in the brain. Tissue availability of dipeptide carnosine for brain tissue is relatively good and constitutes 59% from the total amount of blood carnosine. It was found that the maximum concentration of carnosine in the brain occurs at the sixth hour after i.p. administration when the concentration of drug in the blood is minimal.
Assuntos
Química Encefálica/efeitos dos fármacos , Encéfalo/metabolismo , Carnosina/farmacologia , Carnosina/farmacocinética , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de TempoRESUMO
Anticonvulsant activity and pharmacokinetics of nanoemulsion and unmodified substance of carbamazepine were compared in experiments on mice. Carbamazepine nanoemulsion demonstrated significant anticonvulsant activity and was superior to unmodified substance of carbamazepine against seizures induced by maximum electric shock and picrotoxin. Relative bioavailability of carbamazepine after administration of nanoemulsion was 160% compared to unmodified substance. Carbamazepine nanoemulsion more effectively penetrated through BBB by 1.5 times in comparison with unmodified substance.
Assuntos
Anticonvulsivantes/farmacologia , Anticonvulsivantes/farmacocinética , Dietilcarbamazina/farmacologia , Dietilcarbamazina/farmacocinética , Emulsões/farmacologia , Emulsões/farmacocinética , Convulsões/tratamento farmacológico , Animais , Disponibilidade Biológica , Barreira Hematoencefálica/metabolismo , Dietilcarbamazina/administração & dosagem , Estimulação Elétrica , Emulsões/administração & dosagem , Masculino , Camundongos , Nanoestruturas/administração & dosagem , Picrotoxina/toxicidade , Convulsões/induzido quimicamente , Estatísticas não ParamétricasRESUMO
We have experimentally studied pathways of elimination of an oximized derivative of phytoflavonoid pinostrobine by HPLC/mass spectrometry. Four potential metabolites of pinostrobine oxime have been found and there was an attempt to determine their molecular structures on the basis of their fragmentation under positive electrospray ionization conditions. It is established that pinostrobine oxime is removed from the organism mainly unchanged and also in the form of glucuronated derivative.
Assuntos
Antioxidantes/metabolismo , Flavanonas/urina , Oximas/urina , Substâncias Protetoras/metabolismo , Animais , Antioxidantes/química , Antioxidantes/farmacocinética , Biotransformação , Flavanonas/química , Flavanonas/farmacocinética , Glucuronatos/urina , Masculino , Oximas/química , Oximas/farmacocinética , Substâncias Protetoras/química , Substâncias Protetoras/farmacocinética , Ratos , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
The effect of lipid nanocomplexes loaded with acetylsalicylic acid (aspirin) on platelet aggregation in vitro was investigated. The antithrombotic effect of aspirin in complex with liposomes prepared from pig brain glycosphingolipids is not only significantly higher compared to control, but also accompanied by leveling of the development of proaggregant effects. It was shown that ADP-induced platelet aggregation is reduced by the introduction of electrostatic charge in the structure of lipid bilayer of liposomes. The effect achieved for the liposomes possessing a negative charge was more pronounced in comparison to the effect of positively charged liposomes.