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1.
Pharm Dev Technol ; 26(7): 740-749, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34182861

RESUMO

This work mainly studies the interfacial behaviors of scutellarin on a newly developed emulsion and establishes a three-phase distribution model. The results showed that the concentration of scutellarin could decrease the interfacial tension and the gel-liquid crystal phase transition temperature of phospholipids. By observing the micromorphology of the emulsion, it is inferred that the drug exists on the emulsion interface. The distribution of drugs in three phases at different pH was calculated. The results showed that when pH was in the range of 3.0-8.0, the content of scutellarin in the oil phase was less than 0.25%; when pH < 7.4, more than 88% of the drugs were on the interface; when pH > 7.4, the drugs were mainly distributed in the aqueous phase. Therefore, the behavior of emulsions (pH 6.0) in vitro and in vivo is mainly composed of the behavior of drugs on the interface. The study above can explain some properties of the emulsions after loading scutellarin. Including the decrease of particle size and stability constant Ke, the increase of zeta potential, and the decreased chemical stability after the pH value went higher.


Assuntos
Apigenina/administração & dosagem , Estabilidade de Medicamentos , Emulsões/química , Glucuronatos/administração & dosagem , Apigenina/química , Apigenina/farmacocinética , Composição de Medicamentos , Emulsões/farmacocinética , Glucuronatos/química , Glucuronatos/farmacocinética , Humanos , Concentração de Íons de Hidrogênio , Tensão Superficial
2.
Zhong Yao Cai ; 37(7): 1262-5, 2014 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-25566664

RESUMO

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.


Assuntos
Fenômenos Químicos , Flavonoides/química , Lipossomos , Temperatura
3.
AAPS PharmSciTech ; 14(2): 861-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23649996

RESUMO

This study aimed to develop and evaluate a novel multi-unit tablet that combined a pellet with a sustained-release coating and a tablet with a pulsatile coating for the treatment of circadian rhythm diseases. The model drug, isosorbide-5-mononitrate, was sprayed on microcrystalline cellulose (MCC)-based pellets and coated with Eudragit(®) NE30D, which served as a sustained-release layer. The coated pellets were compressed with cushion agents (a mixture of MCC PH-200/ MCC KG-802/PC-10 at a ratio of 40:40:20) at a ratio of 4:6 using a single-punch tablet machine. An isolation layer of OpadryII, swellable layer of HPMC E5, and rupturable layer of Surelease(®) were applied using a conventional pan-coating process. Central-composite design-response surface methodology was used to investigate the influence of these coatings on the square of the difference between release times over a 4 h time period. Drug release studies were carried out on formulated pellets and tablets to investigate the release behaviors, and scanning electron microscopy (SEM) was used to monitor the pellets and tablets and their cross-sectional morphology. The experimental results indicated that this system had a pulsatile dissolution profile that included a lag period of 4 h and a sustained-release time of 4 h. Compared to currently marketed preparations, this tablet may provide better treatment options for circadian rhythm diseases.


Assuntos
Angina Pectoris/tratamento farmacológico , Fármacos Cardiovasculares/química , Transtornos Cronobiológicos/tratamento farmacológico , Dinitrato de Isossorbida/análogos & derivados , Administração Oral , Fármacos Cardiovasculares/administração & dosagem , Celulose/análogos & derivados , Celulose/química , Química Farmacêutica , Preparações de Ação Retardada , Portadores de Fármacos , Excipientes/química , Derivados da Hipromelose , Dinitrato de Isossorbida/administração & dosagem , Dinitrato de Isossorbida/química , Cinética , Metacrilatos/química , Metilcelulose/análogos & derivados , Metilcelulose/química , Microscopia Eletrônica de Varredura , Polímeros/química , Solubilidade , Comprimidos , Tecnologia Farmacêutica/métodos
4.
Yao Xue Xue Bao ; 48(5): 759-66, 2013 May.
Artigo em Chinês | MEDLINE | ID: mdl-23888702

RESUMO

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.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Ácido Láctico/química , Ácido Poliglicólico/química , Preparações de Ação Retardada , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Nanopartículas , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Tecnologia Farmacêutica
5.
Drug Dev Ind Pharm ; 38(6): 653-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22468612

RESUMO

AIM: The aim of this study was to investigate the feasibility of cationic biodegradable dextran microspheres loaded with bovine serum albumin (BSA) posterior to gel formation (postloading). METHOD: 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 and net positive surface charge increased with increasing amounts of DMAEMA. Loading efficiency of dextran microspheres for BSA was analyzed through fluorescence microscopy and measured. The BSA release from the cationic dextran microspheres in vitro was investigated. RESULTS: BSA could penetrate into cationic dextran microspheres, but neutral dextran microspheres could not. Protein-loading efficiency (98.1--100%) by postloading was higher compared with by preloading (60.2--75.9%), when the incubated protein concentration was below 1.5 mg/ml. Even though BSA is incorporated in the hydrogel network based on electrostatic interaction, a controlled release can be achieved by varying the initial network density of the microspheres. CONCLUSION: These findings suggest that it is a feasible method to prepare dextran microspheres with high surface-charge density to efficiently adsorb oppositely charged protein based on electrostatic interactions.


Assuntos
Implantes Absorvíveis , Dextranos/química , Sistemas de Liberação de Medicamentos , Microesferas , Proteínas/química , Soroalbumina Bovina , Animais , Bovinos , Géis/química , Géis/metabolismo , Tamanho da Partícula , Proteínas/metabolismo , Eletricidade Estática , Propriedades de Superfície
6.
Pharmazie ; 67(8): 706-11, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22957436

RESUMO

OBJECTIVE: To compare the pulmonary absorption characteristics of two insulin solutions-humalog (insulin lispro) and Novolin R (Biosynthetic Human insulin) with in vivo and in vitro methods. METHODS: Investigate the pharmacodynamics in Sprague Dawley (SD) rat model (in vivo studies) and permeability across Rana catesbeiana pulmonary membrane (in vitro studies) of Biosynthetic Human insulin (BHI) and insulin lispro (LI) at different doses. RESULTS: Both of the insulins could reduce blood glucose levels promptly after pulmonary administration. But LI showed a better tendency on hypoglycemic effect than BHI in the in vivo studies. In the in vitro studies, the apparent permeability coefficient (Papp) for BHI and LI were almost constant with increasing concentrations, which implied that insulin maybe passively diffuse through the Rana catesbeiana pulmonary membrane barrier. Interestingly, the Papp of LI was obviously higher than that of BHI, indicating that the permeability of LI across Rana catesbeiana pulmonary membrane was more effective than that of BHI. CONCLUSION: These in vitro and in vivo results suggested that LI was easier to be absorbed in the lung than BHI and Rana catesbeiana pulmonary membrane had a potential ability, as a transport model, to predict in vivo pulmonary absorption of insulin.


Assuntos
Hipoglicemiantes/farmacocinética , Insulina Lispro/farmacocinética , Pulmão/metabolismo , Absorção , Algoritmos , Animais , Área Sob a Curva , Glicemia/metabolismo , Impedância Elétrica , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Técnicas In Vitro , Indicadores e Reagentes , Injeções Espinhais , Insulina Lispro/administração & dosagem , Insulina Lispro/farmacologia , Masculino , Membranas/metabolismo , Permeabilidade , Soluções Farmacêuticas , Rana catesbeiana , Ratos , Ratos Sprague-Dawley
7.
Pharmazie ; 67(5): 448-51, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22764580

RESUMO

Natural pulmonary surfactant (PS) and its artificial substitute phospholipid hexadecanol tyloxapol (PHT) are effective absorption enhancers on promoting recombinant human insulin (Rh-ins) absorption in vivo, but the in vitro efficacy and underlying mechanism remains unclear. In the current study, the permeation promoting effects of PS and PHT of insulin through Calu-3 monolayers in Transwell were evaluated. The viability of Calu-3 cells on conducting the permeation study was confirmed by TER and Electron Microscopy. Both PS and PHT significantly enhanced the permeation of Rh-ins and FD4 through calu-3 cells, with PS having a greater absorption enhancing effect than that of PHT. PS and PHT may interact directly with the tight junctions between cells and then result in intercellular permeation of peptide drugs. LDH release assay showed no significant acute toxicity of PS and PHT. The results indicated that these absorption enhancing agents may be useful as an absorption enhancer for pulmonary delivery of peptide and protein drugs.


Assuntos
Insulina/metabolismo , Pulmão/metabolismo , Fosfolipídeos/farmacologia , Surfactantes Pulmonares/farmacologia , Absorção , Linhagem Celular , Linhagem Celular Tumoral , Células Epiteliais/metabolismo , Corantes Fluorescentes , Humanos , L-Lactato Desidrogenase/metabolismo , Microscopia Eletrônica de Transmissão , Permeabilidade , Proteínas Recombinantes/metabolismo , Sais de Tetrazólio , Tiazóis , Junções Íntimas/metabolismo
8.
AAPS PharmSciTech ; 13(3): 961-6, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22752681

RESUMO

This study set out to develop a novel and stable nanoemulsion formulation of natural vitamin E with increased oral bioavailability. The natural vitamin E nanoemulsion was prepared by a modified emulsification technique. The physicochemical characteristics of natural vitamin E nanoemulsion were characterized and its pharmacokinetics study was performed as well. The experimental results showed droplet diameters ranging from 20 to 400 nm (average, 87.7 nm) with a negative electrostatic potential (-23.5 ± 1.5 mv). The pharmacokinetics study of this nanoemulsion and corresponding soft capsule was carried out using noncompartment model method. Compared with the marketed soft capsule, the C (max) of the natural vitamin E nanoemulsion was higher, while the T (max) was shorter. Thus, plasma concentration-time profiles in rats dosed with nanoemulsion showed a 1.6-fold enhancement in the area under the curve of natural vitamin E compared with the marketed soft capsule. The antioxidative effects of the natural vitamin E nanoemulsion and the marketed soft capsule were also evaluated by the levels of superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration in serum and liver tissue. According to the SOD activity and the MDA concentration determined, the nanoemulsion was superior to the marketed soft as an antioxidative agent. The overall results demonstrated that the nanoemulsion drug delivery system could be a promising strategy for the delivery of natural vitamin E, which showed great potential for clinical application.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Vitamina E/administração & dosagem , Vitamina E/metabolismo , Administração Oral , Animais , Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos/tendências , Masculino , Ratos , Ratos Sprague-Dawley
9.
Yao Xue Xue Bao ; 47(10): 1384-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23289153

RESUMO

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.


Assuntos
Força Compressiva , Dinâmica não Linear , Pós/química , Pressão
10.
Zhong Yao Cai ; 35(9): 1500-7, 2012 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-23451507

RESUMO

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.


Assuntos
Portadores de Fármacos/química , Nanotubos de Carbono/química , Verapamil/administração & dosagem , Verapamil/química , Preparações de Ação Retardada , Estudos de Viabilidade , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Transmissão , Nanotecnologia/métodos , Nanotubos de Carbono/ultraestrutura , Solubilidade , Temperatura , Verapamil/metabolismo
11.
Yao Xue Xue Bao ; 46(1): 115-20, 2011 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-21465817

RESUMO

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).


Assuntos
Eletrólitos/química , Óxido Ferroso-Férrico/química , Rodaminas/administração & dosagem , Soroalbumina Bovina/administração & dosagem , Carbonato de Cálcio/química , Cápsulas , Precipitação Química , Portadores de Fármacos , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos , Nanopartículas de Magnetita , Microscopia Eletrônica de Varredura , Microscopia de Fluorescência , Tamanho da Partícula , Rodaminas/química , Soroalbumina Bovina/química
12.
Yao Xue Xue Bao ; 46(8): 990-6, 2011 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-22007526

RESUMO

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.


Assuntos
Quitosana/química , Mióticos/administração & dosagem , Pilocarpina/administração & dosagem , Absorção , Animais , Área Sob a Curva , Disponibilidade Biológica , Córnea/metabolismo , Emulsões , Microscopia Eletrônica de Transmissão , Mióticos/química , Mióticos/farmacocinética , Soluções Oftálmicas , Tamanho da Partícula , Pilocarpina/química , Pilocarpina/farmacocinética , Coelhos , Distribuição Aleatória , Solubilidade , Lágrimas/metabolismo
13.
Acta Biochim Biophys Sin (Shanghai) ; 42(6): 410-7, 2010 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-20539941

RESUMO

A new bacterial secondary messenger, bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP), is usually synthesized or decomposed by proteins containing GGDEF or glutamate-alanine-leucine (EAL) domain. They often act as cyclase or phosphodiesterase of c-di-GMP and their genes are distributed among almost all bacteria according to known genomic DNA sequences. However, the systematic identification of GGDEF and EAL genes remains unclear in rhizobia, soil bacteria that interact with compatible legumes to form nitrogen-fixing nodules. In this study, 19 putative GGDEF and EAL genes were identified in a model rhizobium, Sinorhizobium meliloti, by bioinformatic analysis (encoding 5 GGDEF proteins, 4 EAL proteins, and 10 GGDEF and EAL double-domain proteins). Null mutants of 14 genes were constructed through systematic plasmid insertion. All 14 gene mutants showed deficient growth in minimal medium and defective motility, and 11 gene mutants produced a lot more exopolysaccharide and displayed less competitive nodulation on the host plant, alfalfa. Our results suggested that GGDEF and EAL proteins may play different roles in the control of S. meliloti physiology, although they contain conserved catalytic (GGDEF or EAL) domains. Our finding also implied that c-di-GMP may play an important role in the interactions between this rhizobium and its host plants to establish efficient symbiosis.


Assuntos
Proteínas de Bactérias/fisiologia , GMP Cíclico/análogos & derivados , Medicago sativa/microbiologia , Polissacarídeos Bacterianos/biossíntese , Sinorhizobium meliloti/fisiologia , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , GMP Cíclico/metabolismo , Regulação Bacteriana da Expressão Gênica , Medicago sativa/genética , Medicago sativa/metabolismo , Nodulação/genética , Estrutura Terciária de Proteína/genética , Sistemas do Segundo Mensageiro/genética , Sinorhizobium meliloti/genética , Sinorhizobium meliloti/crescimento & desenvolvimento
14.
Chem Pharm Bull (Tokyo) ; 58(11): 1455-60, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21048336

RESUMO

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.


Assuntos
Portadores de Fármacos/química , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Flavonoides/administração & dosagem , Flavonoides/farmacocinética , Lipídeos/química , Miocárdio/metabolismo , Animais , Estabilidade de Medicamentos , Medicamentos de Ervas Chinesas/química , Emulsões/química , Flavonoides/química , Injeções Intravenosas , Camundongos , Tamanho da Partícula , Solubilidade
15.
Chem Pharm Bull (Tokyo) ; 58(12): 1612-6, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21139264

RESUMO

The purpose of the present study was to evaluate the enhancement effect of the natural pulmonary surfactant (PS) or its artificial substitute, phospholipid hexadecanol tyloxapol (PHT) on the bioavailability and hypoglycemic activity of recombinant human insulin (rh-insulin) in a pulmonary delivery system. PS- or PHT-loaded insulin formulation was administered to streptozotocin induced diabetic rats, at doses of 5 U/kg, 10 U/kg and 20 U/kg insulin, respectively. The hypoglycemic effect caused by PS or PHT containing rh-insulin was analyzed and the area above the curves (AAC) of serum glucose levels versus time, the minimum glucose concentration (C(min)), the time to C(min) (T(min)) and the pharmacological availability (PA%) were derived from the serum glucose profiles. Results showed that PS and PHT caused significantly decrease in serum glucose levels. The decrease in plasma glucose levels continued for about 5 h after the nadir. The highest AAC value was obtained when 20 U/kg rh-insulin with PS or PHT as absorption enhancer was administered to rats. AAC(0-360 min) of PS- or PHT-loaded rh-insulin was 2-3 times as much as that without PS or PHT and PA% increased by 1.3-2 fold. Thus, the extent of oral absorption of insulin from PS- or PHT-loaded particles was significantly greater when compared with that without them. In addition, PHT as well as PS did not change the lactate dehydrogenase (LDH) activity, alkaline phosphatase (AKP) activity and N-acetyl-ß-D-glucoaminidase (NAG) activity in bronch fluid which are sensitive indicators of acute toxicity to lung cells in bronchoalveolar lavage (BAL). It is concluded that PS and PHT is a promising absorption enhancer for pulmonary delivery systems of large molecule drugs as rh-insulin.


Assuntos
Hipoglicemiantes/farmacocinética , Insulina/farmacocinética , Fosfolipídeos/química , Polietilenoglicóis/química , Surfactantes Pulmonares/química , Tensoativos/química , Absorção , Acetilglucosaminidase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Glicemia/análise , Química Farmacêutica , Diabetes Mellitus Experimental/tratamento farmacológico , Vias de Administração de Medicamentos , Humanos , Hidroliases/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina/genética , Insulina/uso terapêutico , Lesão Pulmonar/metabolismo , Pós/química , Ratos , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo , Traqueia
16.
Drug Dev Ind Pharm ; 36(6): 657-65, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20136497

RESUMO

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.


Assuntos
Ácidos e Sais Biliares/síntese química , Hidrocarbonetos Clorados/síntese química , Fígado/metabolismo , Polietilenoglicóis/síntese química , Polímeros/síntese química , Animais , Ácidos e Sais Biliares/administração & dosagem , Ácidos e Sais Biliares/sangue , Sistemas de Liberação de Medicamentos/métodos , Hidrocarbonetos Clorados/administração & dosagem , Hidrocarbonetos Clorados/sangue , Lipossomos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/metabolismo , Polímeros/administração & dosagem , Polímeros/metabolismo , Ratos , Ratos Wistar
17.
Pharmazie ; 65(7): 467-70, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20662312

RESUMO

The purpose of the present study was to prepare multivesicular liposomes (MVL) with a high drug loading capacity for intramuscular sustained release and to investigate their potential applicability towards tramadol, and to improve the stability of liposomes by coating PEG. The basic physiochemical properties of tramadol MVLs and PEG-coated MVLs were studied. The average particle sizes of optimum preparation were 18.2 microm and 31.3 microm. The entrapment efficiency was up to 80%. The encapsulation efficiency of tramadol MVLs and PEG-coated MVLs was measured. The results confirmed the possibility of multivesicular liposomes as a sustained-release delivery system. Tramadol was continuously released from MVL formulations in PBS (pH 6.8) in vitro, and reached a maximum of 80% within 72 h. The results show that tramadol PEG-coated MVLs could provide sustained release according to the first order kinetic equation.


Assuntos
Analgésicos Opioides/química , Tramadol/química , Analgésicos Opioides/administração & dosagem , Preparações de Ação Retardada , Portadores de Fármacos , Composição de Medicamentos , Estabilidade de Medicamentos , Indicadores e Reagentes , Lipossomos , Tamanho da Partícula , Excipientes Farmacêuticos , Polietilenoglicóis , Solubilidade , Tramadol/administração & dosagem
18.
J Integr Plant Biol ; 52(7): 639-52, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20590994

RESUMO

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.


Assuntos
Proteínas de Ligação ao GTP/fisiologia , Regulação da Expressão Gênica de Plantas , Medicago truncatula/genética , Medicago truncatula/microbiologia , Proteínas de Plantas/fisiologia , Simbiose/fisiologia , Sequência de Aminoácidos , Proteínas de Ligação ao GTP/química , Proteínas de Ligação ao GTP/genética , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Dados de Sequência Molecular , Proteínas de Plantas/química , Proteínas de Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/microbiologia , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/microbiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rhizobium/genética , Homologia de Sequência de Aminoácidos , Sinorhizobium meliloti/crescimento & desenvolvimento , Sinorhizobium meliloti/fisiologia , Simbiose/genética
19.
Yao Xue Xue Bao ; 45(3): 371-5, 2010 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-21351515

RESUMO

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).


Assuntos
Carbonato de Cálcio/química , Eletrólitos/química , Fluoresceína-5-Isotiocianato/análogos & derivados , Ouro/química , Soroalbumina Bovina/química , Cápsulas , Portadores de Fármacos , Sistemas de Liberação de Medicamentos/métodos , Fluoresceína-5-Isotiocianato/química , Microscopia Eletrônica de Varredura , Microscopia de Fluorescência , Nanopartículas , Tamanho da Partícula
20.
Yao Xue Xue Bao ; 45(1): 120-5, 2010 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-21351461

RESUMO

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.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Humor Aquoso/metabolismo , Córnea/efeitos dos fármacos , Flurbiprofeno/análogos & derivados , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Disponibilidade Biológica , Córnea/citologia , Emulsões , Feminino , Flurbiprofeno/administração & dosagem , Flurbiprofeno/efeitos adversos , Flurbiprofeno/farmacocinética , Géis , Masculino , Nanopartículas , Soluções Oftálmicas , Coelhos , Reologia , Viscosidade
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