RESUMO
The aim of this study was to evaluate the pharmacokinetics and tissue distribution of the glycyrrhetinic acid (GA) liposome modified with galactosylated lipid (NOH-GA-LP), compared with GA conventional liposome (GA-LP) and GA solution in mice. The pharmacokinetics and biodistribution of liposomal and solution formulation of GA in mice were studied after intravenous administration. Plasma and tissues were treated using liquid-liquid extraction and determined using reversed-phase high-performance liquid chromatography. Results showed that the mean residence times of NOH-GA-LP (2.99-fold) and GA-LP (2.94-fold) were higher than that of the GA solution in plasma. NOH-GA-LP produced a drug concentration in the liver that was markedly higher than that in other tissues and was approximately 2.0- and 4.8-fold of that of GA-LP and GA solution, respectively. In conclusion, the NOH-GA-LP prepared in this study is a promising sustained-release and drug-targeting system for antitumor drugs.
Assuntos
Galactose/química , Ácido Glicirretínico/administração & dosagem , Ácido Glicirretínico/farmacocinética , Lipídeos/química , Lipossomos/química , Lipossomos/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Preparações de Ação Retardada , Galactose/administração & dosagem , Ácido Glicirretínico/química , Rim/metabolismo , Lipídeos/administração & dosagem , Lipossomos/administração & dosagem , Fígado/metabolismo , Pulmão/metabolismo , Camundongos , Miocárdio/metabolismo , Baço/metabolismo , Distribuição TecidualRESUMO
Strain M(438), deposited as CGMCC3917 and isolated from inoculums of bacterial cellulose (BC) producing strain screened in homemade vinegar and then induced by high hydrostatic pressure treatment (HHP), has strong ability to produce BC more than three times as that of its initial strain. It is the highest yield BC-producing strain ever reported. In this paper, M(438) was identidied as Gluconacetobacter hansenii subsp. nov. on the basis of the results obtained by examining it phylogenetically, phenotypically, and physiologically-biochemically. Furthermore, the genetic diversity of strain M(438) and its initial strain was examined by amplified fragment length polymorphism. The results indicated that strain M(438) was a deletion mutant induced by HHP, and the only deleted sequence showed 99% identity with 24,917-24,723 bp in the genome sequence of Ga. hansenii ATCC23769, and the complement gene sequence was at 24,699-25,019 bp with local tag GXY_15142, which codes small multidrug resistance (SMR) protein. It can be inferred that SMR might be related to inhibiting BC production to a certain extent.
Assuntos
Celulose/biossíntese , Gluconacetobacter/química , Gluconacetobacter/metabolismo , Sequência de Aminoácidos , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Gluconacetobacter/classificação , Gluconacetobacter/genética , Pressão Hidrostática , Dados de Sequência Molecular , Filogenia , Alinhamento de SequênciaRESUMO
In this study, NOH (NOH = N-octadecyl-4-[(D-galactopyranosyl)oxy]-2,3,5,6-tetrahydroxy hexanamide) was enzymatically synthesized as a targeting molecule and incorporated into liposomes to prepare a liposome surface modified with galactose. Glycyrrhetinic-acid-loaded liposome (GA-LP) and glycyrrhetinic-acid-loaded liposome surface modified with galactose (NOH-GA-LP) were prepared by the ethanol-injection method. NOH-GA-LP was characterized by morphology, particle size, zeta potential, encapsulation efficiency, release in vitro, and stability. The size of spherical particles was in the range of 179-211 nm. Spherical particles exhibit a positive electrical charge (38.7 mV) and possess high encapsulation efficiency (91.3%) and show sustained release (72% over 48 hours) in vitro. This novel approach for the liposome surface modified with galactose by enzymatic synthesis is expected to provide potential application as a drug carrier for active targeted delivery to hepatocytes.