RESUMO
The mechanism for anti-tumor activity of oridonin (ORI) nanosuspension, prepared by the high pressure homogenization method, was studied using MCF-7 human breast carcinoma cells in vitro. MTT assay, observation of morphologic changes, flow cytometric analysis, and western blot analysis indicated that ORI nanosuspension could significantly intensify the in vitro anti-tumor activity to MCF-7 cells, as compared with ORI solution. Furthermore, ORI nanosuspension induced G2/M stage proliferation arrest and apoptosis in MCF-7 cells depending on its concentration. In addition, western blot analysis indicated that the pro-caspase-3 protein was not cleaved into the activated form and the expression of anti-apoptotic Bcl-2 protein decreased, on the contrary, the expression of pro-apoptotic Bax protein increased in a dose-dependent manner in ORI nanosuspension-treated cells. These observations indicated that the anti-tumor activity of ORI nanosuspension was intensified by cell-cycle arrest and apoptosis induction.
Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Diterpenos do Tipo Caurano/administração & dosagem , Nanopartículas/administração & dosagem , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Caspase 3/genética , Caspase 3/metabolismo , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Diterpenos do Tipo Caurano/química , Relação Dose-Resposta a Droga , Feminino , Fase G2/efeitos dos fármacos , Humanos , Nanopartículas/química , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Suspensões/administração & dosagem , Suspensões/química , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Nanostructured lipid carriers (NLC) are a new generation of lipid nanoparticles, which are produced by controlled mixing of solid lipids with spatially incompatible liquid lipids leading to special nanostructures with improved drug incorporation and release properties. In this study, silybin-loaded nanostructured lipid carriers with various liquid lipid content were successfully prepared by the method of emulsion evaporation at a high temperature and solidification at a low temperature. The size and morphology of nanoparticles were significantly influenced by the liquid lipid content. As the liquid lipid content increased to 20 wt%, the obtained particles showed distinguished smaller size. Compared with solid lipid nanoparticles (SLN), NLC presented improved drug loading capacity which increased with increasing the liquid lipid content. The differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis indicated that the incorporation of liquid lipids could interfere with the crystallization of solid lipids. The drug in vitro release behavior from NLC displayed a biphasic drug release pattern with burst release at the initial stage and prolonged release afterwards, and the successful controlled release rate can be achieved by controlling the liquid lipid content.
Assuntos
Portadores de Fármacos/química , Lipídeos/química , Nanopartículas/química , Silimarina/administração & dosagem , Varredura Diferencial de Calorimetria , Composição de Medicamentos , Microscopia Eletrônica de Transmissão , Estrutura Molecular , Tamanho da Partícula , Silibina , Silimarina/química , Solubilidade , Estearatos/química , Propriedades de Superfície , Triglicerídeos/química , Difração de Raios XRESUMO
AIM: To investigate the tissue distribution and pharmacokinetics of oridonin-solid lipid nanoparticles in animals. METHODS: HPLC method was established to determine the concentration of oridonin in serum of rabbits and in different tissues of mice. The results after tail iv administration of oridonin and oridonin solid lipid nanoparticles were compared. RESULTS: The relative tissue content of oridonin of solid lipid nanoparticles in the liver, spleen, lung, heart and kidney were 4.25%, 3.44%, 1.19%, 0.52% and 0.60%, respectively. The concentration-time curves of oridonin and oridonin solid lipid nanoparticles were both fitted to the three-compartment model. T(1/2)pi = 0.087 h, T(1/2)alpha = 1.65 h, T(1/2)beta = 32.36 h, V(C) = 0.66 mL.kg(-1). CONCLUSION: Solid lipid nanoparticles could increase the hepatic and lienic targeting efficiency of oridonin in mice and improve its bioavailability. Solid lipid nanoparticles were helpful for oridonin to reach a long circulation time and were hopeful to be its novel drug carrier.
