RESUMEN
OBJECTIVE: To prepare breviscapine pro-liposomes and evaluate its properties and stability, as well as its interaction with the mimic-membrane. METHODS: Breviscapine liposomes were prepared by thin film-lyophilization method. Phase inversion temperature was measured by electrical conductance method and coalescence kinetics was studied. Water/n-octanol trans-membrane diffusion model was designed to study the dynamic distribution behavior between two phases, through the determination of diffusion rate of breviscapine and liposomes. RESULTS: The phase inversion temperature was 63 degrees C, the activity energy for coalescence was 14.66 kJ/mol. The results suggested that breviscapine from liposomes staying on the interface were found more than the breviscapine infusion. CONCLUSION: Breviscapine liposomes prepared with thin film-lyophilization method have good physicochemical properties and stability, which is beneficial to treatment.
Asunto(s)
Fenómenos Químicos , Flavonoides/química , Liposomas , TemperaturaRESUMEN
Doxorubicin-loaded PLGA nanoparticles (DOX-PLGA NPs) was prepared by double emulsion (W/O/W) solvent evaporation method with the biodegradable materials-poly (lactic-co-glycolic acid) (PLGA) used as carrier materials. Single-factor test was used to investigate the influence of the type and ratio of the organic phase, the amount of surfactant, PLGA concentration, the ratio of external water phase and oil phase (W/O), the ratio of doxorubicin and PLGA, ultrasonic time and stirring time on the preparation of nanoparticles. The best formulation and preparation conditions were optimized by orthogonal test based on single-factor test, evaluation indicator as particle size and entrapment efficiency, and the results were analyzed by overall desirability. And the in vitro release behaviors of the nanoparticles were studied as well. The size distribution, zeta potential, morphology of DOX-PLGA NPs were characterized by laser light scattering and transmission electron microscopy; encapsulation efficiency and releasing behavior of DOX-PLGA NPs in vitro were investigated by ultraviolet spectrophotometry. The results show that the DOX-PLGA NPs are regularly spherical in shape with the mean size of (189.2 +/- 5.3) nm, and the zeta-potential of the NPs is about (-28.32 +/- 0.52) mV. Drug loading and encapsulation efficiency are estimated to be (73.16 +/- 0.43) % and (1.51 +/- 0.07) %, respectively. The cumulative percentage of the drug released is 90.34%, and the in vitro release behavior made up of initial burst release and sustained-release could be described by the bidirectional kinetic equation. The results indicate that hydrophilic small-molecule drugs could be successfully entrapped into PLGA-NPs. With optimization of the formulation and preparation conditions, we obtained uniform and stable DOX-PLGA NPs with sustained release character in vitro and pH-sensitive property, which could provide the experimental basis for the development of a new anti-tumor sustained-release formulation.
Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Portadores de Fármacos/química , Ácido Láctico/química , Ácido Poliglicólico/química , Preparaciones de Acción Retardada , Microscopía de Fuerza Atómica , Microscopía Electrónica de Transmisión , Nanopartículas , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Tecnología FarmacéuticaRESUMEN
OBJECTIVE: The aim of this study was to load Verapamil Hydrochloride to carboxylated multi-walled carbon nanotubes( c-CNTs) and discuss the mechanism of drug release which could act as an effective basis for c-MWNTs used as drug carriers of controlled and sustained release delivery system. METHODS: Raw CNTs were treated with mixed strong acid to obtain c-CNTs. Raman, IR, SEM and HR-TEM were used to characterize the CNTs and investigate the loading sites for drugs. The release behavior of the drug delivery system in vitro and the release model were studied. RESULTS: The raw CNTs were successfully grafted with carboxyl group by acid treatment. The water-soluble ability of c-CNTs was greatly improved. The length of c-CNTs was 200-300nm. Meanwhile, the ends of c-CNTs were opened. The results of the drug loading experiment showed that the more adding drugs, the larger loading content of drugs. Most of the drugs were loaded into the inner pores of c-CNTs when adding drugs was no more than 0.1 as quantity as c-CNTs. As the quantity of adding drugs increased, the drugs were loaded both in the inner pores and on the out-wall of c-CNTs. The release results in vitro showed release mechanism had something with the quantity of adding drugs. CONCLUSION: C-CNTs can be used as carriers of sustained and controlled release delivery system. Ideal release behavior of drugs can be achieved by choosing appropriate formula.
Asunto(s)
Portadores de Fármacos/química , Nanotubos de Carbono/química , Verapamilo/administración & dosificación , Verapamilo/química , Preparaciones de Acción Retardada , Estudios de Factibilidad , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Transmisión , Nanotecnología/métodos , Nanotubos de Carbono/ultraestructura , Solubilidad , Temperatura , Verapamilo/metabolismoRESUMEN
A new mathematical equation characterizing the compression of pharmaceutical materials is presented. This equation presumed that the rate of change of the compressible volume of powder with respect to the pressure is proportional to the compressible volume. The new model provided a good fit to several model substances employing non-linear regression techniques. The validity of the model had been verified with experimental results of various pharmaceutical powders according to the Akaikes informatics criterion (AIC) and the sum of squared deviations (SS). The parameter of the new model might reflect quantitatively the fundamental compression behaviors of the powders. It had demonstrated that the proposed model could well predict the compaction characteristics of solid particles like the Kawakita model.
Asunto(s)
Fuerza Compresiva , Dinámicas no Lineales , Polvos/química , PresiónRESUMEN
The study is to design chitosan-coated pilocarpine nitrate submicro emulsion (CS-PN/SE) for the development of a novel mucoadhesive submicro emulsion, aiming to prolong the precorneal retention time and improve the ocular absorption. CS-PN/SE was fabricated in two steps: firstly, pilocarpine nitrate submicro emulsion (PN/SE) was prepared by high-speed shear with medium chain triglycerides (MCT) as oil phase and Tween 80 as the main emulsifier, and then incubated with chitosan (CS) acetic solution. The preparation process was optimized by central composite design-response surface methodology. Besides the particle size, zeta potential, entrapment efficiency and micromorphology were investigated, CS-PN/SE's precorneal residence properties and miotic effect were especially studied using New Zealand rabbits as the animal model. When CS-PN/SE was administered topically to rabbit eyes, the ocular clearance and the mean resident time (MRT) of pilocarpine nitrate were found to be dramatically improved (P < 0.05) compared with PN/SE and pilocarpine nitrate solution (PNs), since the K(CS-PN/SE) was declined to 0.006 4 +/- 0.000 3 min(-1) while MRT was prolonged up to 155.4 min. Pharmacodynamics results showed that the maximum miosis of CS-PN/SE was as high as 46.3%, while the miotic response lasted 480 min which is 255 min and 105 min longer than that of PNs and PN/SE, respectively. A larger area under the miotic percentage vs time curve (AUC) of CS-PN/SE was exhibited which is 1.6 folds and 1.2 folds as much as that of PNs and PN/SE, respectively (P < 0.05). Therefore, CS-PN/SE could enhance the duration of action and ocular bioavailability by improving the precorneal residence and ocular absorption significantly.
Asunto(s)
Quitosano/química , Mióticos/administración & dosificación , Pilocarpina/administración & dosificación , Absorción , Animales , Área Bajo la Curva , Disponibilidad Biológica , Córnea/metabolismo , Emulsiones , Microscopía Electrónica de Transmisión , Mióticos/química , Mióticos/farmacocinética , Soluciones Oftálmicas , Tamaño de la Partícula , Pilocarpina/química , Pilocarpina/farmacocinética , Conejos , Distribución Aleatoria , Solubilidad , Lágrimas/metabolismoRESUMEN
In this study, polyelectrolyte microcapsules have been fabricated by biocompatible ferrosoferric oxide nanoparticles (Fe3O4 NPs) and poly allyamine hydrochloride (PAH) using layer by layer assembly technique. The Fe3O4 NPs were prepared by chemical co-precipitation, and characterized by transmission electron microscopy (TEM) and infrared spectrum (IR). Quartz cell also was used as a substrate for building multilayer films to evaluate the capability of forming planar film. The result showed that Fe3O4 NPs were selectively deposited on the surface of quartz cell. Microcapsules containing Fe3O4 NPs were fabricated by Fe3O4 NPs and PAH alternately self-assembly on calcium carbonate microparticles firstly, then 0.2 molL(-1) EDTA was used to remove the calcium carbonate. Scanning electron microscopy (SEM), Zetasizer and vibrating sample magnetometer (VSM) were used to characterize the microcapsule's morphology, size and magnetic properties. The result revealed that Fe3O4 NPs and PAH were successfully deposited on the surface of CaCO3 microparticles, the microcapsule manifested superparamagnetism, size and saturation magnetization were 4.9 +/- 1.2 microm and 8.94 emu x g(-1), respectively. As a model drug, Rhodamin B isothiocyanate labeled bovine serum albumin (RBITC-BSA) was encapsulated in microcapsule depended on pH sensitive of the microcapsule film. When pH 5.0, drug add in was 2 mg, the encapsulation efficiency was (86.08 +/- 3.36) % and the drug loading was 8.01 +/- 0.30 mg x m(L-1).
Asunto(s)
Electrólitos/química , Óxido Ferrosoférrico/química , Rodaminas/administración & dosificación , Albúmina Sérica Bovina/administración & dosificación , Carbonato de Calcio/química , Cápsulas , Precipitación Química , Portadores de Fármacos , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos , Nanopartículas de Magnetita , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Tamaño de la Partícula , Rodaminas/química , Albúmina Sérica Bovina/químicaRESUMEN
Breviscapine lipid emulsions were prepared by a high speed dispersion-homogenization method with optimal formulation and technological method. The proportion of liposomes in breviscapine lipid emulsions, an important character for determining the behavior of drug in vivo belongs to which carriers, was less than 5%. Loading breviscapine into lipid emulsions did increase the breviscapine concentrations in plasma, retarded the clearance, and exhibited the properties of sustained-release concluded by pharmacokinetic parameters: after bolus administration, the elimination phase (t(1/2(ß)) = 99.535) of lipid emulsions was 5.4-times longer than that of Injectio Breviscapine. The AUC(0â∞) (14.453-times), k(10) (0.047-times), Cl(s) (0.147-times), and MRT(0â∞) (17.766-times) values also confirmed this trend. The amount of drug in every tissue increased at different levels after intravenous administration of breviscapine lipid emulsions compared with Injectio Breviscapine. The relative exposure value of breviscapine lipid emulsions for plasma and lungs were 29.59 and 5.81, respectively, indicating that the exposure of breviscapine to plasma and lungs was significantly increased by entrapment in lipid emulsions. Other targeting evaluation indexes also proved the superiority of lipid emulsions carrier to deliver drug to the targeting region of vascular and lung diseases therapy.
Asunto(s)
Flavonoides/química , Flavonoides/farmacocinética , Lípidos/química , Animales , Química Farmacéutica/métodos , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/síntesis química , Preparaciones de Acción Retardada/química , Sistemas de Liberación de Medicamentos/métodos , Emulsiones/administración & dosificación , Emulsiones/síntesis química , Emulsiones/química , Emulsiones/farmacocinética , Flavonoides/administración & dosificación , Inyecciones Intravenosas/métodos , Lípidos/administración & dosificación , Liposomas/administración & dosificación , Liposomas/química , Ratones , Tamaño de la Partícula , Tensoactivos/administración & dosificación , Tensoactivos/química , Distribución TisularRESUMEN
Breviscapine is a Traditional Chinese Medicine treating cardiovascular diseases by promoting blood circulation and removing blood stasis. The major active component of breviscapine has low aqueous solubility, poor chemical stability, short biological half-life and rapid elimination rate from the plasma. The use of a lipid emulsion formulation containing breviscapine might improve chemical stability, increase drug loading, exhibit sustained release profile. In the present study, we developed an optimized formulation and technological method for the preparation of sterile and stable breviscapine lipid emulsion (Bre-LE) for intravenous infusion. The average particle size, polydispersity index, zeta potential, stability constant (K(s)) value and content of final product were (225.3±8.8) nm, 0.221±0.020, (-29.6±1.5) mV, (24.3±2.9)% and (94.5±0.6)% respectively (n=3). The results of in vitro release experiment suggest that lipid emulsion as breviscapine carrier showed a desirable sustained release profile. Dilution stability and long-term stability were also researched in the present paper. The results show the carrier could protect drug from degradation after dilution by phosphate buffered saline and fetal calf serum. And Bre-LE was stable for up to 6 months at room temperature storage condition. The biodistribution of drug in heart of mice increased dramatically after encapsulation into lipid emulsion which was beneficial to heart disease therapy.
Asunto(s)
Portadores de Fármacos/química , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacocinética , Flavonoides/administración & dosificación , Flavonoides/farmacocinética , Lípidos/química , Miocardio/metabolismo , Animales , Estabilidad de Medicamentos , Medicamentos Herbarios Chinos/química , Emulsiones/química , Flavonoides/química , Inyecciones Intravenosas , Ratones , Tamaño de la Partícula , SolubilidadRESUMEN
Sinorhizobium meliloti can live as a saprophyte in soil or as a nitrogen-fixing symbiont inside the root nodule cells of alfalfa and related legumes by utilizing different organic compounds as its carbon source. Here we have identified the matPQMAB operon in S. meliloti 1021. Within this operon, matP, matQ and the M region of the fused gene matMA encode an extracytoplasmic solute receptor, a small transmembrane protein and a large transmembrane protein, consisting of three components of the tripartite ATP-independent periplasmic (TRAP) transporter for malonate transport. The A region of the fused gene matMA and matB encode malonate-metabolizing enzymes, malonyl-CoA decarboxylase and malonyl-CoA synthetase. The null mutant of each matPQMAB gene is unable to grow on M9 minimal medium containing malonate as the sole carbon source. However, these mutants can induce the formation of efficient nitrogen-fixing root nodules on alfalfa. The matPQMAB operon is expressed in free-living bacterial cells and symbiotic bacterial cells from infection threads and root nodules. The GntR family transcriptional regulator, GtrA, specifically binds the promoter of the matPQMAB operon, positively regulating its expression. Moreover, the matPQMAB can be transcriptionally induced by malonate. These results suggested that a C(3)-dicarboxylic acid TRAP transporter is responsible for malonate transport in S. meliloti.
Asunto(s)
Transportadores de Ácidos Dicarboxílicos/genética , Regulación Bacteriana de la Expresión Génica , Malonatos/metabolismo , Operón , Sinorhizobium meliloti/metabolismo , Factores de Transcripción/metabolismo , Aldehído Oxidorreductasas/genética , Aldehído Oxidorreductasas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Carboxiliasas/genética , Carboxiliasas/metabolismo , Coenzima A Ligasas/genética , Coenzima A Ligasas/metabolismo , Transportadores de Ácidos Dicarboxílicos/metabolismo , Genes Bacterianos , Transporte Iónico , Medicago sativa/microbiología , Fijación del Nitrógeno/genética , Plásmidos , Reacción en Cadena de la Polimerasa , ARN Bacteriano , Sinorhizobium meliloti/genética , Sinorhizobium meliloti/crecimiento & desarrollo , Simbiosis/genética , Factores de Transcripción/genéticaRESUMEN
ROPs (Rho-related GTPases of plants) are small GTPases that are plant-specific signaling proteins. They act as molecular switches in a variety of developmental processes. In this study, seven cDNA clones coding for ROP GTPases have been isolated in Medicago truncatula, and conserved and divergent domains are identified in these predicted MtROP proteins. Phylogenetic analysis has indicated that MtROPs are distributed into groups II, III, IV but group I. MtROP genes are expressed in various tissues at different levels. A quantitative reverse transcription PCR analysis indicated that these MtROP genes have different expression profiles in the roots in response to infection with rhizobia. The expression of MtROP3, MtROP5 and MtROP6 are increased, as the expression of Nod factor or rhizobial-induced marker genes--NFP, Rip1 and Enod11; MtROP10 has showed enhanced expression at a certain post-inoculation time point. No significant changes in MtROP7 and MtROP9 expression have been detected and MtROP8 expression is dramatically decreased by about 80%-90%. Additionally, ROP promoter-GUS analysis has showed that MtROP3, MtROP5 and MtROP6 have elevated expression in transgenic root hairs after rhizobial inoculation. These results might suggest a role for some ROP GTPases in the regulation of early stages during rhizobial infection in symbiosis.
Asunto(s)
Proteínas de Unión al GTP/fisiología , Regulación de la Expresión Génica de las Plantas , Medicago truncatula/genética , Medicago truncatula/microbiología , Proteínas de Plantas/fisiología , Simbiosis/fisiología , Secuencia de Aminoácidos , Proteínas de Unión al GTP/química , Proteínas de Unión al GTP/genética , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Datos de Secuencia Molecular , Proteínas de Plantas/química , Proteínas de Plantas/genética , Raíces de Plantas/genética , Raíces de Plantas/microbiología , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/microbiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rhizobium/genética , Homología de Secuencia de Aminoácido , Sinorhizobium meliloti/crecimiento & desarrollo , Sinorhizobium meliloti/fisiología , Simbiosis/genéticaRESUMEN
PURPOSE: The objective of this study was to achieve a sustained and targeted delivery of liposome to the liver, by modifying the phospholipid [phosphatidylcholine (PC)/cholesterol (10 : 1) liposomes with a novel polymer bile salts-(polyethylene glycol)(2000)-bile salts (BP(2)B). METHODS: First, we generated a novel BP(2)B by N,N'-dicyclohexylcarbodiimide/4-dimethylaminopyridine esterification method and confirmed by Fourier transform infraredand (1) H-NMR spectra. Second, we prepared the BP(2)B-modified liposomes (BP(2)BL) that included BP(2)B, and the effect of the weight ratios of BP(2)B/PC on entrapment efficiency was investigated and BP(2)B/PC = 3% (w/w) was determined as the optimum ratio for the 4,4'-dimethoxy-5,6,5',6'-bi (methylenedioxy)-2,2'-bicarbomethoxybiphenyl liposomes. And then, the ability of the liver target of BP(2)BL was studied by calculating the targeted parameters. RESULTS AND DISCUSSION: All the results revealed that the introduction of polyoxyethylene chains could control interactions of bile salt moieties on liposome surfaces with the receptor compared with traditional liposomes (CL), marking BP(2)BL as a suitable carrier for hepatic parenchymal cell-specific and sustained targeting. It was suggested that liposomes containing such novel BP(2)B have great potential as drug delivery carriers for the liver-selective targeting that has targeted and sustained drug delivery.
Asunto(s)
Ácidos y Sales Biliares/síntesis química , Hidrocarburos Clorados/síntesis química , Hígado/metabolismo , Polietilenglicoles/síntesis química , Polímeros/síntesis química , Animales , Ácidos y Sales Biliares/administración & dosificación , Ácidos y Sales Biliares/sangre , Sistemas de Liberación de Medicamentos/métodos , Hidrocarburos Clorados/administración & dosificación , Hidrocarburos Clorados/sangre , Liposomas , Hígado/efectos de los fármacos , Masculino , Ratones , Polietilenglicoles/administración & dosificación , Polietilenglicoles/metabolismo , Polímeros/administración & dosificación , Polímeros/metabolismo , Ratas , Ratas WistarRESUMEN
The aim of the study is to prepare flurbiprofen axetil nanoemulsion-in situ gel system (FBA/NE-ISG) and observe its ocular pharmacokinetics, rheological behavior, TEM images, irritation and cornea retention. Production of nanoemulsion was based on high-speed shear and homogenization process, and then mixed with gellan gum to prepare FBA/NE-ISG. Rheological study showed that FBA/NE-ISG possesses strong gelation capacity and its viscosity and elastic modulus increases by 2 Pa*s and 5 Pa respectively when mixed with artificial tear at the ratio of 40 : 7. TEM images suggested no significant changes in particle morphology of the pre and post gelation. Good ocular compatibility of FBA/NE-ISG was testified by the irritation test based on histological examination. In vivo fluorescence imaging system was applied to investigate the characteristics of cornea retention, and the results indicated that the nanoemulsion-in situ gel (NE-ISG) prolonged the cornea retention time significantly since K(NE-ISG) (0.008 5 min(-1) was much lower compared with flurbiprofen sodium eye drops (FB-Na, 0.03% w/v) of which the K(Eye drops) was 0.105 2 min(-1), indicated that the cornea retention time of NE-ISG was prolonged significantly. Pharmacokinetics of FBA/NE-ISG in rabbit aqueous humor was studied by cornea puncture, the MRT (12.3 h) and AUC(0-12h) (126.8 microg x min x mL(-1)) of FBA/NE-ISG was 2.7 and 2.9 times higher than that of the flurbiprofen sodium eye drops respectively, which meant that the ocular bioavailability was improved greatly by the novel preparation. Therefore, FBA/NE-ISG can enhance the ocular bioavailability by prolonging drug corneal retention significantly. What's more, encapsulated by emulsion droplets prodrug flurbiprofen (FBA) instead of flurbiprofen (FB) can reduce the ocular irritation.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacocinética , Humor Acuoso/metabolismo , Córnea/efectos de los fármacos , Flurbiprofeno/análogos & derivados , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Disponibilidad Biológica , Córnea/citología , Emulsiones , Femenino , Flurbiprofeno/administración & dosificación , Flurbiprofeno/efectos adversos , Flurbiprofeno/farmacocinética , Geles , Masculino , Nanopartículas , Soluciones Oftálmicas , Conejos , Reología , ViscosidadRESUMEN
In this work, polyelectrolyte microcapsules containing gold nanoparticles were prepared via layer by layer assembly. Gold nanoparticles and poly (allyamine hydrochloride) (PAH) were coated on the CaCO3 microparticles. And then EDTA was used to remove the CaCO3 core. Scanning electron microscopy (SEM) was used to characterize the surface of microcapsules. SEM images indicate that the microcapsules and the polyelectrolyte multilayer were deposited on the surface of CaCO3 microparticles. FITC-bovine serum albumin (FITC-BSA, 2 mg) was incorporated in the CaCO3 microparticles by co-precipitation. Fluorescence microscopy was used to observe the fluorescence intensity of microcapsules. The encapsulation efficiency was (34.31 +/- 2.44) %. The drug loading was (43.75 +/- 3.12) mg g(-1).
Asunto(s)
Carbonato de Calcio/química , Electrólitos/química , Fluoresceína-5-Isotiocianato/análogos & derivados , Oro/química , Albúmina Sérica Bovina/química , Cápsulas , Portadores de Fármacos , Sistemas de Liberación de Medicamentos/métodos , Fluoresceína-5-Isotiocianato/química , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Nanopartículas , Tamaño de la PartículaRESUMEN
The aim of this study is to prepare cationic biodegradable dextran microspheres loaded with tetanus toxoid (TT) and to investigate the mechanism of protein loading. Positively charged microspheres were prepared by polymerization of hydroxylethyl methacrylate derivatized dextran (dex-HEMA) and dimethyl aminoethyl methacrylate (DMAEMA) in an aqueous two-phase system. The loading of the microspheres with TT was based on electrostatic attraction. The net positive surface charge increased with increasing amounts of DMAEMA. Confocal images showed fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) could penetrate into cationic dextran microspheres but not natural dextran microspheres. TT loading efficiency by post-loading was higher compared with by pre-loading. Even though TT is incorporated in the hydrogel network based on electrostatic interaction, still a controlled release can be achieved by varying the initial network density of the microspheres.
Asunto(s)
Dextranos/química , Metacrilatos/química , Toxoide Tetánico/administración & dosificación , Preparaciones de Acción Retardada , Portadores de Fármacos/química , Hidrogeles/química , Microscopía Confocal , Microesferas , Tamaño de la Partícula , Polimerizacion , Albúmina Sérica Bovina/química , Toxoide Tetánico/químicaRESUMEN
Dry powder inhalers (DPIs) have received considerable attention because of their propellant-free composition and stability. DPIs include the DPI devices and inhalation powders. The purpose of this review is to address the development of the DPIs, including the mechanisms of absorption, the products, the devices, the preparation technology, and the characteristics.
Asunto(s)
Sistemas de Liberación de Medicamentos , Inhaladores de Polvo Seco , Pulmón , Administración Tópica , Tecnología Farmacéutica/métodosRESUMEN
Microcrystalline cellulose (MCC), calcium phosphate (DCP)/MCC (4:1, w/w) and lactose (Lac)/MCC (4:1) pellets with different intragranular porosity were prepared in an extrusion-spheronizator and three volume ratios of ethanol/water were used as binder agents to prepare pellets. The compression behaviors of these pellets with different intragranular pore volume were evaluated with the parameters of Kawakita model. The results showed that high pore volume of pellets made up of MCC had the best compressibility and low pore volume of pellets had a poor compactibility. However, the compressibility of different porosity of pellets made up of DCP/MCC (4:1) or Lac/MCC (4:1) was good, but they were not significantly different. The reason might be the main compression mechanism of high porosity of MCC pellets was plastic deformation and that of DCP/MCC pellets or Lac/MCC pellets was not plastic deformation but fragmentation. These results can be observed directly by the SEM photographs. According to these results, the conclusion could be drawn that high porosity MCC pellets and different porosity DCP/MCC pellets and Lac/MCC pellets can be used as cushion granules to maintain the original shape and release characteristics of drug pellets when pellets were tabletted.
Asunto(s)
Fosfatos de Calcio/química , Celulosa/química , Composición de Medicamentos/métodos , Lactosa/química , Comprimidos , Excipientes , Microesferas , Porosidad , PresiónRESUMEN
To develop different methods for determining siRNA content and the entrapment efficiency of siRNA loaded liposomes, SYBR Gold electrophoresis method and Ribogreen fluorospectrophotometry method were used respectively. SYBR Gold electrophoresis method has a good linear relation in a range at 0.2-2.0 micromol x L(-1) (R = 0.9930), and the recovery at the high, middle and low concentrations were 96.35%, 96.92%, and 100.74%, respectively (n = 3). The intra-day and inter-day RSD were far below 5% (n = 5). Ribogreen fluorospectrophotometry method has a good linear relation in a range at 10-50 nmol x L(-1) (R = 0.9971), and the recovery at the high, middle and low concentrations were 98.22%, 99.88% and 99.64%, respectively (n = 3). The intra-day and inter-day RSD were far below 5% (n = 5). The content and the entrapment efficiency of three batches of siRNA cationic liposomes were 98.52%, 97.85% and 99.20%, 96.45%, respectively, with these two methods. And there is no significant difference by ANOVA. Both of the two methods are accurate, sensitive, convenient method for determination of the siRNA content and the entrapment efficiency of siRNA loaded cationic liposomes.
Asunto(s)
Sistemas de Liberación de Medicamentos , Liposomas/química , ARN Interferente Pequeño/análisis , Portadores de Fármacos , Electroforesis , Espectrometría de FluorescenciaRESUMEN
To prepare verapamil hydrochloride (VH) core-in-cup tablets with tri-layered tablet and four-layered tablet as core tablets, separately, which can provide biphasic release with double-pulsatile and multi-phasic release, core tablets were prepared by direct compression method, and core-in-cup tablets by dry-compression coated technology. The parameter, time-lag (T(lag)), was used to evaluate the influence of factors, such as the weight of the top cover layer, the amount of hydroxypropylmethylcellulose (HPMC), and the compression load on VH release. With the increase of the weight and HPMC amount of the top cover layer, the first lag time T(lag1) was prolonged. The second lag time T(lag2) of core-in-cup tablet with four-layered tablet as core tablet increased with the increasing amount of HPMC K100M. With the increase of compression load among the range (6 - 10 kg x cm(-2)), the two lag times were prolonged. Core-in-cup tablets with double-pulsatile and multi-phasic release released VH after the first lag time (4 -5 h), then kept sustained release for 12 h or 13 h, finally released rapidly. The drug in the core-in-cup tablet only released from the top cover layer. T(lag) is determined by the erosion rate of the inhibitor layers (the top cover layer and the sustained-release layer of the multi-layer core tablet).
Asunto(s)
Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos , Metilcelulosa/análogos & derivados , Verapamilo/administración & dosificación , Preparaciones de Acción Retardada , Portadores de Fármacos , Excipientes/química , Derivados de la Hipromelosa , Metilcelulosa/química , ComprimidosRESUMEN
The aim was to prepare a novel ocular cationic microemulsion-in situ gel (CM-ISG) system with vitamin A palmitate (VAP) as model drug, and investigate the corneal retention behavior and corneal irritation of the system. VAP/CM was prepared by a process based on supply of energy, and the before-and-after gelation rheology of VAP/CM-ISG was investigated. In vitro VAP release and gel dissolution of both VAP/CM-ISG and Oculotect Gel was determined. And in vitro corneal retention behavior of both formulations was evaluated by captive bubble technique. Ocular irritation test was carried out based on the Draize method. Images of TEM showed that homogenous VAP/CM was made, and no significant differences of particle size were found between the VAP/CM and VAP/CM in Poloxamer 407 gel. Rheology study illustrated that VAP/CM reduced the phase transition temperature of Poloxamer 407 gel by 1.5 degrees C, and the elastic modulus increased about 15.7 times. The in vitro release and gel dissolution profile of both formulations exhibited the characteristics of zero order kinetics. Comparing with Oculotect Gel, desorption kinetics study of VAP/CM-ISG exhibited longer corneal retention time and smaller contact angle. Irritation test showed a good ocular compatibility of VAP/CM-ISG. Therefore, VAP/CM-ISG combined both advantages of the cationic microemulsion and in situ gel system, provided better wettability and longer ocular retention time. It might be a promising ocular drug delivery system.
Asunto(s)
Córnea/metabolismo , Sistemas de Liberación de Medicamentos , Vitamina A/análogos & derivados , Animales , Córnea/efectos de los fármacos , Preparaciones de Acción Retardada , Diterpenos , Portadores de Fármacos , Emulsiones , Soluciones Oftálmicas , Poloxámero/química , Conejos , Distribución Aleatoria , Ésteres de Retinilo , Viscosidad , Vitamina A/administración & dosificación , Vitamina A/farmacocinética , Vitamina A/toxicidadRESUMEN
In nonplant species, many heat-shock transcription factors (HSFs) undergo spatiotemporal-specific alternative splicing. However, little is known about the spatiotemporal-specific splicing of HSFs in plants. Previously, we reported that the alfalfa HSF gene MsHSF1 undergoes multiple alternative splicing events in various tissues. Here, we identified another spliced transcript isoform, MsHSF1c, containing a 177-base tandem repeat, and showed that the low-abundance MsHSF1c is a nodule-specific transcript of MsHSF1. We also found that MsHSF1 presents multiple alleles with single-base variations and the expression of MsHSF1 alleles has allele-specific differences in alfalfa nodules. Because single-base variations at position 1006 change the AT of MsHSF1b to GT in MsHSF1b-3, creating a pair of donor/acceptor sites with the AG of MsHSF1b/1b-1 at position 827-828 for pre-mRNA splicing, we suggest that MsHSF1c may be generated by trans-splicing between alleles MsHSF1b-3 and MsHSF1b or MsHSF1b-1. These results provide new insight into the role of tissue-specific contribution in the transcription of plant HSF genes.