RESUMO
Sponge-type nanocarriers (spongosomes) are produced upon dispersion of a liquid crystalline sponge phase formed by self-assembly of an amphiphilic lipid in excess aqueous phase. The inner organization of the spongosomes is built-up by randomly ordered bicontinuous lipid membranes and their surfaces are stabilized by alginate chains providing stealth properties and colloidal stability. The present study elaborates spongosomes for improved encapsulation of Brucea javanica oil (BJO), a traditional Chinese medicine that may strongly inhibit proliferation and metastasis of various cancers. The inner structural organization and the morphology characteristics of BJO-loaded nanocarriers at varying quantities of BJO were determined by cryogenic transmission electron microscopy (Cryo-TEM), small angle X-ray scattering (SAXS) and dynamic light scattering (DLS). Additionally, the drug loading and drug release profiles for BJO-loaded spongosome systems also were determined. We found that the sponge-type liquid crystalline lipid membrane organization provides encapsulation efficiency rate of BJO as high as 90%. In vitro cytotoxicity and apoptosis study of BJO spongosome nanoparticles with A549 cells demonstrated enhanced anti-tumor efficiency. These results suggest potential clinical applications of the obtained safe spongosome formulations.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Brucea/química , Portadores de Fármacos/química , Portadores de Fármacos/síntese química , Nanopartículas/química , Óleos/administração & dosagem , Óleos/farmacologia , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Óleos/química , Tamanho da Partícula , Relação Estrutura-Atividade , Propriedades de SuperfícieRESUMO
Bioavailability of baicalin (BAI), an example of traditional Chinese medicine, has been modified by loading into liposome. Several liposome systems of different composition i.e., lipid/cholesterol (L), long-circulating stealth liposome (L-PEG) and folate receptor (FR)-targeted liposome (L-FA) have been used as the drug carrier for BAI. The obtained liposomes were around 80 nm in diameter with proper zeta potentials about -25 mV and sufficient physical stability in 3 months. The entrapment efficiency and loading efficiency of BAI in the liposomes were 41.0-46.4% and 8.8-10.0%, respectively. The morphology details of BAI lipsosome systems i.e., formation of small unilamellar vesicles, have been determined by cryogenic transmission electron microscopy (cryo-TEM) and small angle X-ray scattering (SAXS). In vitro cytotoxicity of BAI liposomes against HeLa cells was evaluated by MTT assay. BAI loaded FR-targeted liposomes showed higher cytotoxicity and cellular uptake compared with non-targeted liposomes. The results suggested that L-FA-BAI could enhance anti-tumor efficiency and should be an effective FR-targeted carrier system for BAI delivery.
Assuntos
Flavonoides/química , Ácido Fólico/análogos & derivados , Lipossomos/química , Polietilenoglicóis/química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Microscopia Crioeletrônica , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Feminino , Flavonoides/farmacocinética , Flavonoides/farmacologia , Receptores de Folato com Âncoras de GPI/antagonistas & inibidores , Receptores de Folato com Âncoras de GPI/metabolismo , Ácido Fólico/química , Células HeLa , Humanos , Lipossomos/ultraestrutura , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Espalhamento a Baixo Ângulo , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Difração de Raios XRESUMO
A new method for copper-catalyzed P-C bond formation through reaction of phosphorus nucleophiles with diaryliodonium salts at room temperature is described. Most target products are obtained with this method in high yields within a short reaction time of 10 min. It can be easily adapted to large-scale preparations. When unsymmetrical iodonium salts are employed, nucleophilic substitution occurs preferentially on the sterically hindered aromatic ring or the more electron-deficient ring.