RESUMO
To study the alkaloids from Melodinus moraei,seven compounds were separated and purified by column chromatography over silica gel, reverse phase silica gel and preparative HPLC. Their chemical structures were elucidated by MS and spectral data (1H-NMR, 13C-NMR) as scandine(1),tabersonine(2),melodinine N(3),melodinine P(4), melodinine T(5),19-epimeloscandonine(6),16-hydroxy-19S-vindolinine(7). Compounds 1-7 were isolated from M. moraei for the first timeï¼The bioassays showed all tested samples displayed antitumor activity against the cell lines such as A549,PC-3,HGC-27 and HL-60.
Assuntos
Alcaloides/química , Apocynaceae/química , Medicamentos de Ervas Chinesas/química , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Compostos Fitoquímicos/química , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
Chemical constituents of 95% ethanol extract of the dried persistent calyx of Physalis pubescens were investigated. By chromatography on a silica gel column and reverse-phase preparative HPLC, 10 compounds were isolated from the dichloromethane fraction. Based on the MS and 1D/2D NMR data, these compounds were identified as 5-O-(E-feruloyl) blumenol (1), isovanillin (2), (E) -ethyl 3-(4-hydroxyphenyl) acrylate (3), 4-hydroxybenzaldehyde(4), 4-methylphenol (5), (E) -methyl cinnamate (6), 7,3',4' trimethoxyquercetin (7), 5,3', 5'-trihydroxy-3,7,4'-trimethoxyflavone(8), danielone (9), and 5,5'-diisobutoxy-2,2'-bifuran (10).
Assuntos
Medicamentos de Ervas Chinesas/química , Physalis/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/isolamento & purificação , Estrutura Molecular , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
BACKGROUND: The objective of this research was to design an effective gene delivery system composed of cationic solid lipid nanoparticles (SLNs), protamine, and Deoxyribonucleic acid DNA. METHODS: Cationic SLNs were prepared using an aqueous solvent diffusion method with octadecylamine as the cationic lipid material. First, protamine was combined with DNA to form binary protamine/DNA nanoparticles, and the ternary nanoparticle gene delivery system was then obtained by combining binary protamine/DNA nanoparticles with cationic SLNs. The size, zeta potential, and ability of the binary and ternary nanoparticles to compact and protect DNA were characterized. The effect of octadecylamine content in SLNs and the SLNS/DNA ratios on transfection efficiency, cellular uptake and cytotoxicity of the ternary nanoparticles were also assessed using HEK293 cells. RESULTS: When the weight ratio of protamine to DNA reached 1.5:1, the plasmid DNA could be effectively compacted and protected. The average hydrodynamic diameter of the ternary nanoparticles when combined with protamine increased from 188.50 ± 0.26 nm to 259.33 ± 3.44 nm, and the zeta potential increased from 25.50 ± 3.30 mV to 33.40 ± 2.80 mV when the weight ratio of SLNs to DNA increased from 16/3 to 80/3. The ternary nanoparticles showed high gene transfection efficiency compared with Lipofectamine™ 2000/DNA nanoparticles. Several factors that might affect gene transfection efficiency, such as content and composition of SLNs, post-transfection time, and serum were examined. The ternary nanoparticles composed of SLNs with 15 wt% octadecylamine (50/3 weight ratio of SLNs to DNA) showed the best transfection efficiency (26.13% ± 5.22%) in the presence of serum. It was also found that cellular uptake of the ternary nanoparticles was better than that of the SLN/DNA and binary protamine/DNA nanoparticle systems, and DNA could be transported to the nucleus. CONCLUSION: SLNs enhanced entry of binary protamine/DNA nanoparticles into the cell, and protamine protected DNA from enzyme degradation and transported DNA into the nucleus. Compared with Lipofectamine 2000/DNA nanoparticles, these cationic ternary nanoparticles showed relatively durable and stable gene transfection in the presence of serum.
Assuntos
DNA/química , Nanopartículas/química , Protaminas/química , Transfecção/métodos , Aminas/química , Cátions , Sobrevivência Celular , DNA/genética , DNA/metabolismo , DNA/farmacocinética , Ensaio de Desvio de Mobilidade Eletroforética , Células HEK293 , Humanos , Lipídeos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Microscopia de Fluorescência , Tamanho da PartículaRESUMO
PURPOSE: Safe and effective lipid nanoemulsion (LNE) formulations for the antitumor delivery of doxorubicin is designed. METHODS: LNEs composed of medium-chain triglyceride, soybean oil, lecithin, and doxorubicin are prepared by a solvent-diffusion method in an aqueous system. The effects of lipid material composition and polyethylene glycol (PEG)ylation on the size, drug encapsulation efficiency, and stability of LNEs are investigated. Based on in-vitro cytotoxicity and cellular uptake tests of A549 (human lung carcinoma) cells, in-vivo biodistribution, antitumor activity, and cardiac toxicity are further examined using nude mouse bearing A549 tumor. RESULTS: The LNE size decreases from 126.4 ± 8.7 nm to 44.5 ± 9.3 nm with increased weight ratio of medium-chain triglyceride to soybean oil from 1:4 to 3:2, whereas the encapsulation efficiency of doxorubicin is slightly reduced from 79.2% ± 2.1% to 71.2% ± 2.9%. The PEGylation of LNE by 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(PEG)2000] (DSPE-PEG 2000) does not significantly change the size and drug encapsulation efficiency. Three-month storage at room temperature and lyophilization process does not affect the drug encapsulation efficiency, whereas the size slightly increases to almost 100 nm. The in-vitro drug-release profiles of LNEs suggest that the present formulation can prolong drug release for 48 hours. LNEs can be internalized into tumor cells in vitro and efficiently accumulate in tumor tissues in vivo by passive targeting. Analysis results of in-vitro and in-vivo antitumor activities reveal that doxorubicin-loaded LNE exerts a therapeutic effect similar to that of the commercial Adriamycin. Moreover, the toxicity of doxorubicin, particularly its cardiac toxicity, is reduced. CONCLUSION: The present LNE formulation of doxorubicin can effectively suppress tumor growth and improve the safety of Adriamycin.
Assuntos
Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos/química , Emulsões/química , Nanopartículas/química , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Estabilidade de Medicamentos , Coração/efeitos dos fármacos , Humanos , Lipídeos/química , Camundongos , Camundongos Nus , Miocárdio/patologia , Tamanho da Partícula , Polietilenoglicóis/química , Distribuição Tecidual , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
To reduce the side effects and drug resistance in cancer chemotherapy, we have examined the in vitro efficacy of the combination of paclitaxel (PTX) and doxorubicin (DOX) loaded in nanosized polymeric micelles with glycolipid-like structure, which formed by lipid grafted chitosan. The cytotoxicities of PTX and DOX, either as single agents or in combination, were examined using drug sensitive tumor cells and drug resistant cells. It was found that the 50% inhibition of cellular growth (IC(50)) of PTX and DOX in micelles against drug sensitive cells was lowered about 20-fold and 4-7-fold compared to that of Taxol and DOX solution, respectively. The IC(50) of PTX and DOX in micelles against drug resistant cells was lowered more significantly, and no clear difference was found between drug sensitive and drug resistant cells. The coadministration of PTX and DOX in micelles showed a more conspicuous effect than that of micelles loaded with a single drug. The micelles presented excellent internalization to cancer cells, which results in increased intracellular accumulation of PTX and DOX in its molecular-target site. The coadministration of glycolipid-like micelles loaded with different cytotoxic drugs indicated synergistic effects for drug sensitive cells and drug resistant cells.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/química , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Portadores de Fármacos/química , Glicolipídeos/química , Linhagem Celular , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Portadores de Fármacos/administração & dosagem , Humanos , Micelas , Paclitaxel/administração & dosagem , Paclitaxel/químicaRESUMO
In this study, the cytotoxicity of doxorubicin (DOX) loaded stearic acid grafted chitosan oligosaccharide (CSO-SA) micelles and its core modified drug delivery systems were investigated in vitro. The in vitro drug release experiments using cellular culture medium, Roswell Park Memorial Institute 1640 (RPMI-1640) medium as a dissolution medium confirmed that the DOX release from CSO-SA micelles was successfully delayed by the core modification of CSO-SA micelles with stearic acid (SA). The cell viability assay against A549 cells indicated the 50% inhibition concentration (IC(50)) of blank CSO-SA micelles and the core modified CSO-SA micelles was 369 +/- 27 microg/mL and 234 +/- 9 microg/mL, respectively. The entrapment of DOX by CSO-SA micelles could decrease the IC(50) of DOX from 3.5 to 1.9 microg/mL, and a further reduction to 0.7 microg/mL could result by the core modification of CSO-SA micelles. The fluorescence image observations of DOX and DOX concentration measurements inside A549 cells demonstrated that the DOX concentration inside cells was increased by the entrapment of CSO-SA micelles, and further enhanced by the core modification of CSO-SA micelles. The results indicated that the CSO-SA micelles with modified cores could be useful as a drug delivery vehicle for cancer chemotherapy.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Quitosana/química , Doxorrubicina/farmacologia , Portadores de Fármacos , Micelas , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Doxorrubicina/metabolismo , Composição de Medicamentos , Humanos , Concentração Inibidora 50 , Cinética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Tamanho da Partícula , Solubilidade , Ácidos Esteáricos/químicaRESUMO
OBJECTIVE: To evaluate the efficacy and adverse effects of 5-nitroimidazole derivatives in treatment of bacterial vaginosis (BV). METHODS: 278 BV patients were randomly divided into 8 groups to be treated with (1) oral metronidazole sustained release tablet 750 mg/day for 7 days, (2) oral metronidazole sustained release tablet 750 mg/day for 7 days and vaginal tinidazole 250 mg for 7 days, (3) oral tinidazole 1 g/day for 3 days (2 g for the first dose), (4) oral tinidazole 1 g/day for 3 days (2 g for the first dose), (5) oral ornidazole 2 x 500 mg/day for 3 days and vaginal tinidazole 250 mg for 7 days, (6) oral ornidazole 2 x 500 mg/day for 3 days, (7) oral secnidazole 2 g in a single dose and vaginal tinidazole 250 mg for 7 days, and (8) oral secnidazole 2 g in a single dose. RESULTS: The clinical cure rates of the oral administration groups were 56.76% - 62.50%, all significantly lower than those of the oral/vaginal combination groups (80.00% - 86.11%, all P < 0.05). There was nit significantly difference in efficacy level among the only oral treatment groups and the oral/vaginal combination groups (all P > 0.05). CONCLUSION: Combination of oral and vaginal administration of 5-nitroimidazole derivatives is more effective in treatment of BV than oral administration only.
Assuntos
Metronidazol/análogos & derivados , Nitroimidazóis/uso terapêutico , Ornidazol/uso terapêutico , Tinidazol/uso terapêutico , Vaginose Bacteriana/tratamento farmacológico , Administração Intravaginal , Administração Oral , Adulto , Preparações de Ação Retardada , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Metronidazol/administração & dosagem , Metronidazol/uso terapêutico , Nitroimidazóis/administração & dosagem , Ornidazol/administração & dosagem , Estudos Prospectivos , Comprimidos , Tinidazol/administração & dosagem , Resultado do Tratamento , Adulto JovemRESUMO
Amphiphilic stearic acid-grafted chitosan oligosaccharide (CSO-SA) micelles have been shown a good drug delivery system by incorporating hydrophobic drugs into the core of the micelles. One of the problems associated with the use of CSO-SA micelles is disassociation or the initial burst drug release during the dilution of drug delivery system by body fluid. Herein, the core of CSO-SA micelles was modified by the physical solubilization of stearic acid (SA) to reduce the burst drug release and enhance the physical stability of CSO-SA micelles. The CSO-SA micelles had 27.4+/-2.4 nm number average diameter, and indicated pH-sensitive properties. The micelle size and drug release rate from micelles increased with the decrease of pH value. After the incorporation of SA into CSO-SA micelles, the micelle size was increased, and the zeta potential was decreased. The extents of the increase in micelle size and the decrease of zeta potential related with the incorporated amount of SA. The in vitro drug release tests displayed the incorporation of SA into CSO-SA micelles could reduce the drug release from the micelles due to the enhanced hydrophobic interaction among SA, hydrophobic drug and hydrophobic segments of CSO-SA.
Assuntos
Antibióticos Antineoplásicos/química , Quitosana/química , Doxorrubicina/química , Portadores de Fármacos , Micelas , Ácidos Esteáricos/química , Química Farmacêutica , Preparações de Ação Retardada , Composição de Medicamentos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cinética , Tamanho da Partícula , Solubilidade , Tecnologia Farmacêutica/métodosRESUMO
The goal of this research was to prepare a kind of hydrophilic sustained release microspheres of interferon-alpha (IFN-alpha), alginate-chitosan microspheres (ACM) of IFN, and investigate its pharmacokinetics in mice. Alginate microspheres of IFN-alpha were first prepared by an emulsion method and further incubated in chitosan to form IFN-ACM. The influences of isopropanol, bovine serum albumin (BSA), and pH adjustment by isoelectric point of IFN were studied. The optimized IFN-ACM was obtained with smooth and round morphology, size of 2.18 +/- 0.43 microm and entrapment efficiency of 40%. All the concentrations of IFN-alpha were determined by IFN assay kits. Finally the pharmacokinetics of IFN-ACM suspension was studied in ICR mice by intramuscular (I.M.) routes. Compared with IFN solution, C(max) of IFN-ACM reduced 2.3-fold, and time to achievement of maximum serum concentrations (T(max)) increased 4-fold. Meanwhile the area under the concentration-time curve (AUC) was the same as that of solution. The concentration-time profiles presented the prolonged serum levels of IFN from IFN-ACM.
Assuntos
Portadores de Fármacos , Interferon-alfa/farmacocinética , Microesferas , Alginatos/química , Alginatos/metabolismo , Animais , Cápsulas/química , Cápsulas/farmacocinética , Bovinos , Quitosana/química , Quitosana/metabolismo , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Feminino , Ácido Glucurônico/química , Ácido Glucurônico/metabolismo , Ácidos Hexurônicos/química , Ácidos Hexurônicos/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
The aim of this study is to investigate both the effects of hydrophilic additives and combined processing parameters on the in vitro release of a model protein, bovine serum albumin (BSA), from poly(lactic-co-glycolic acid) (PLGA) microspheres. Additives including beta-cyclodextrin, HP-beta-cyclodextrin, poly(ethylene glycol) (PEG) 6000, and sorbitol, and processing parameters such as the poly(vinyl alcohol) (PVA) concentration, emulsification temperature, aqueous/oil phase, evaporation method, and dehydration method were evaluated. PLGA microspheres were all prepared by the double-emulsion solvent extraction/evaporation method, and the results showed that no statistically significant differences of particle sizes and entrapment efficiencies appeared. Interestingly, the initial burst releases were markedly changed by both additives and processing parameters. Initial burst releases were accelerated by hydrophilic additives except for PEG 6000 and were retarded by the formulation composed of higher PVA concentration, tween-20 as an emulsifier in the internal aqueous phase, glycerol in the oil phase, and inorganic salt in the external aqueous phase, and operated at low temperature. Scanning electron microscopy showed that the more porous and dimpled the structure on the surface of the PLGA microspheres, the larger the initial burst release. The microspheres that displayed a relatively smooth and compact surface showed the least burst release.
Assuntos
Portadores de Fármacos , Excipientes/química , Glicolatos/química , Microesferas , Proteínas/química , Tecnologia Farmacêutica , Química Farmacêutica , Ácido Láctico , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Polietilenoglicóis/química , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Porosidade , Soroalbumina Bovina/química , Solubilidade , Sorbitol/química , Propriedades de Superfície , Tecnologia Farmacêutica/métodos , Fatores de Tempo , beta-Ciclodextrinas/químicaRESUMO
OBJECTIVE: To study the adjustment of Xianggui pill on the cytokine of endometriosis model rat, and investigate the mechanism of Xianggui pill on the treatment of endometriosis. METHOD: To set up endometriosis model by rat self-endometria transplantation, drench sodium chloride, Xianggui pill elixation or Danazol after grouping, and to detect the contents of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) by ELISA. RESULT: The contents of IL-8, TNF-alpha in the peripheral blood and peritoneal fluid of model group were higher than that of the blank group; The quality of allotopia growth intima tissue, the quantity of macrophage in peritoneal fluid and the contents of IL-8, TNF-alpha in the Xianggui pill group and Danazol group were all lower than those of the model group; but there was no significant difference of each target between the Xianggui pill group and Danazol group. CONCLUSION: Xianggui pill can restrain significantly the growth of allotopia intima tissue, and has apparently adjustment to the cytokine.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Endometriose/metabolismo , Interleucina-8/metabolismo , Macrófagos Peritoneais/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Contagem de Células , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/isolamento & purificação , Endometriose/sangue , Endometriose/imunologia , Feminino , Interleucina-8/sangue , Macrófagos Peritoneais/patologia , Plantas Medicinais/química , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
AIM: To elevate the encapsulation efficiency, decrease the burst release and improve the release of protein entrapped in poly (lactic-co-glycolic acid) (PLGA) microspheres. The bovine serum albumin (BSA) composite microspheres of alginate-chitosan-PLGA were prepared and the release characteristics of BSA from this composite microspheres were studied. METHODS: The much smaller calcium alginate microcapsules were first prepared by a modified emulsification method in an isopropyl alcohol-washed way and coated with chitosan, then the alginate-chitosan microcapsules were further entrapped in PLGA to form the composite microspheres. The protein concentration was determined using a BCA protein assay kit. The release profiles were changed with various formulation factors. RESULTS: The average diameter of the composite microcapsules was about 30 microm. Comparing with 60% to 70% of the conventional PLGA microspheres, the average encapsulation efficiency was more than 80%, and the burst releases in phosphate buffer solution of the composite microspheres decreased from 40% and 50% to 25% and further to 5% in saline solution. CONCLUSION: The novel composite microspheres were prepared, the drug encapsulation efficiency increased and the burst release decreased. The desired release profiles could be obtained by regulating the ratios of PLG and PLA in the composite microspheres.