RESUMEN

Surfactant and microwave assisted extraction (S-MAE) was used for pectin extraction from orange peel. First, we optimized the conditions of microwave assisted extraction (MAE), e.g., irradiation time, liquid-to-solid ratio (LSR), and pH on pectin yield (PY), galacturonic acid (GA) content, and degree of esterification (DE) using a Box-Behnken design. Under optimal conditions (pH 1.2, 7.0 min, and 21.5 v/w LSR), we obtained a PY of 28.0 ±â€¯0.5%, which was close to the predicted value (31.1%). Second, we analyzed the effect of surfactant on microwave extraction of pectin. Among the surfactants investigated, Tween-80 (8 g/L, w/v) increased PY by 17.0%. Compared with conventional solvent extraction, S-MAE is a novel and efficient method for pectin extraction, which generated a higher (p < 0.05) PY (32.8%), GA content (78.1%), DE (69.8%), and Mw (286.3 kDa).

Asunto(s)

Citrus sinensis/metabolismo , Microondas , Pectinas/química , Tensoactivos/química , Cromatografía Líquida de Alta Presión , Esterificación , Ácidos Hexurónicos/química , Concentración de Iones de Hidrógeno , Pectinas/aislamiento & purificación , Espectroscopía Infrarroja por Transformada de Fourier

RESUMEN

Chitins obtained by fermentation of shrimp wastes using Lactobacillus brevis with and without further inoculations with Rhizopus oligosporus resulted in higher molecular weight than the commercial biopolymer. After grinding in acidic conditions, the attained chitins were fully fibrillated by a mechanical treatment throughout ten passes in a high-pressure water jet system as evidenced by field-emission scanning electron microscopy. The chitin sample crystallinities decreased from 85% to 68%. A previous chitin sample bleaching, as well as the sonication of chitin nanofiber suspensions, enhanced the transparency in the resulting nanofiber sheets. Suspensions and sheets of chitin extracted by L. brevis with successive R. oligosporus inoculations displayed higher transmittance and acetylation degree, as well as improved mechanical properties compared to chitin extracted with only L. brevis. Mechanical studies demonstrated that Young's modulus of the nanofibers using this biological chitin was remarkably higher than that for the commercial product, an important characteristic in polymer reinforcements.

Asunto(s)

Exoesqueleto/química , Quitina/química , Nanofibras/química , Animales , Quitina/aislamiento & purificación , Levilactobacillus brevis , Tamaño de la Partícula , Propiedades de Superficie , Residuos

RESUMEN

The aim of this study was to obtain a stable sunflower oil-in-water (O/W) Pickering emulsion stabilized by chitosan (CS)-stearic acid (SA) nanogels and to compare the oxidative stability of the sunflower Pickering emulsion stabilized by CS-SA nanogels with sunflower oil emulsion stabilized by Tween 80. The results of the scanning electron microscopy revealed that by increasing the SA to CS ratio, the uniformity of particles was increased. Also, the results showed that the emulsions with pH of 8, SA to CS ratio of 0.5:1, and oil-to-nanogel ratio of 20:1 had the highest stability and minimum droplet size. In the following, the oxidative stability of the most favorable Pickering emulsion and the Tween 80-stabilized emulsion was evaluated and compared using the peroxide and thiobarbituric acid tests. The findings implied that the O/W emulsion stabilized by CS-SA nanogels had a higher oxidative stability than the O/W emulsion stabilized by Tween 80.

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Chrysanthemum indicum Linne (C. indicum), a healthy food and folk medicine in China for thousands of years, has been reported to exert heat-clearing and detoxifying effects and extensively applied to treat various symptoms such as inflammation diseases, hepatitis and headache. AIM OF THIS STUDY: The purpose of the present study was to investigate the protective effect of the supercritical carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE) on D-galactose-induced brain and liver damage during aging process and to illuminate the underlying mechanisms. MATERIALS AND METHODS: Mice were orally administrated with CISCFE (100, 150 and 300 mg/kg) after injection with D-galactose. 24 h after the last administration, the blood samples, whole brain and liver tissues were collected for biochemical analysis, histological examination and western blot analysis. The body weight, spleen and thymus indexes, alanine transaminase (ALT), aspartate transaminase (AST), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) in brain and liver, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and necrosis factor-α (TNF-α) were detected. Besides, the expressions of Bax, Bcl-2 and cleaved caspase-3 were determined by western blot assay. RESULTS: The results indicated that CISCFE effectively increased the suppressed body weight, attenuated the decline of thymus and spleen indexes, and reduced the elevated levels of ALT and AST induced by D-gal. Furthermore, CISCFE might notably alleviate D-gal-induced abnormal alterations in structure and function of brain and liver dose-dependently via renewing normal antioxidant enzymes activities (SOD, CAT, GSH-Px), reducing MDA accumulation, decreasing inflammatory cytokines productions (IL-1ß, IL-6, TNF-α), as well as attenuating the increase of Bax/Bcl-2 ratio and cleaved caspase-3 activation in the liver and brain. CONCLUSIONS: Taken together, our present results suggested that CISCFE treatment could effectively mitigate the D-gal-induced hepatic and cerebral injury, and the underlying mechanism might be tightly related to the decreased oxidative stress, inflammation and apoptosis, indicating CISCFE might be an alternative and promising agent for the treatment of aging and age-associated brain and liver diseases.

Asunto(s)

Chrysanthemum/química , Inflamación/prevención & control , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Envejecimiento/patología , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Dióxido de Carbono/química , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Flores , Galactosa/toxicidad , Inflamación/patología , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Extractos Vegetales/administración & dosificación , Superóxido Dismutasa/metabolismo

RESUMEN

Oil-in-water emulsions were prepared with 5% (w/v) carrot-enriched olive oil and stabilized with Tween 80 (TW), phosphatidylcholine (PC), citrus pectin (CP) or a combination of these emulsifiers. Additionally, the methylesterification degree (DM) of citrus pectin was modified, resulting in three different studied pectin structures: CP82, CP38 and CP10. All initial emulsions presented small initial oil droplet sizes and were submitted to an in vitro simulated gastric and small intestinal phase. The latter was executed in a kinetic way to determine the time dependency of the lipolysis reaction, micelle formation and carotenoid bioaccessibility. The results showed that the pectin DM mainly influenced the reaction rate constants, while the emulsifier (combination) determined the extent of lipolysis and carotenoid bioaccessibility. Moreover, a direct relation was observed between the lipolysis reaction and bioaccessibility extent. The presented study showed that targeted emulsion design can be used to tailor lipid digestion kinetics.

Asunto(s)

Carotenoides/farmacocinética , Lipólisis/efectos de los fármacos , Aceite de Oliva/metabolismo , Pectinas/farmacología , Fosfatidilcolinas/farmacología , Disponibilidad Biológica , Carotenoides/química , Emulsionantes/química , Emulsionantes/farmacología , Emulsiones , Cinética , Lípidos/química , Micelas , Fosfatidilcolinas/química

RESUMEN

In foodstuffs, physico-chemical interactions and/or physical constraints between spores, inhibitors and food components may exist. Thus, the objective of this study was to investigate such interactions using a model emulsion as a microbial medium in order to improve bacterial spore control with better knowledge of the interactions in the formulation. Emulsions were prepared with hexadecane mixed with nutrient broth using sonication and were stabilized by Tween 80 and Span 80. The hexadecane ratio was either 35% (v/v) or 50% (v/v) and each emulsion was studied in the presence of organic acid (acetic, lactic or hexanoic) at two pH levels (5.5 and 6). Self-diffusion coefficients of emulsion components and the organic acids were measured by Pulsed Field Gradient-Nuclear Magnetic Resonance (PFG-NMR). The inhibition effect on the spore germination and cell growth of Bacillus weihenstephanensis KBAB4 was characterized by the measure of the probability of growth using the most probable number methodology, and the measure of the time taken for the cells to germinate and grow using a single cell Bioscreen® method and using flow cytometry. The inhibition of spore germination and growth in the model emulsion depended on the dispersed phase volume fraction and the pH value. The effect of the dispersed phase volume fraction was due to a combination of (i) the lipophilicity of the biocide, hexanoic acid, that may have had an impact on the distribution of organic acid between hexadecane and the aqueous phases and (ii) the antimicrobial activity of the emulsifier Tween 80 detected at the acidic pH value. The interface phenomena seemed to have a major influence. Future work will focus on the exploration of these phenomena at the interface.

Asunto(s)

Ácidos/química , Bacillus/crecimiento & desarrollo , Polisorbatos/química , Esporas Bacterianas/crecimiento & desarrollo , Ácido Acético/química , Bacillus/clasificación , Técnicas Bacteriológicas , Caproatos/química , Electroforesis en Gel de Campo Pulsado , Emulsiones , Citometría de Flujo , Microbiología de Alimentos/métodos , Hexosas/química , Concentración de Iones de Hidrógeno , Cinética , Ácido Láctico/química , Esporas Bacterianas/clasificación

RESUMEN

The clinical use of paclitaxel as a chemotherapeutic agent is limited by the severe acute and chronic hypersensitivity caused when it is administered via intraperitoneal or intravenous routes. Thus far, evidence has suggested that transient receptor potential vanilloid-1 (TRPV1) has a key role in the chronic neuropathy induced by paclitaxel. Despite this, the role of TRPV1 in paclitaxel -related acute nociception, especially the development of visceral nociception, has not been evaluated. Thus, the goal of this study was to evaluate the participation of TRPV1 in a model of acute nociception induced by paclitaxel in rats and mice. A single intraperitoneal (i.p.) paclitaxel administration (1 mg/kg, i.p.) produced an immediate visceral nociception response 1 h after administration, caused mechanical and heat hypersensitivity, and diminished burrowing behaviour 24 h after administration. These nociceptive responses were reduced by SB-366791 treatment (0.5 mg/kg, i.p., a TRPV1 antagonist). In addition, TRPV1-positive sensory fibre ablation (using resiniferatoxin, 200 µg/kg, s.c.) reduced visceral nociception and mechanical or heat hypersensitivity caused by paclitaxel injection. Similarly, TRPV1 deficient mice showed a pronounced reduction in mechanical allodynia to paclitaxel acute injection and did not develop heat hypersensitivity. Moreover, 24 h after its injection, paclitaxel induced chemical hypersensitivity to capsaicin (a TRPV1 agonist, 0.01 nmol/site) and increased TRPV1 immunoreactivity in the dorsal root ganglion and sciatic nerve. In conclusion, TRPV1 is involved in mechanical and heat hypersensitivity and spontaneous-pain behaviour induced 24 h after a single paclitaxel injection. This receptor is also involved in visceral nociception induced immediately after paclitaxel administration.

Asunto(s)

Nocicepción/efectos de los fármacos , Paclitaxel/efectos adversos , Canales Catiónicos TRPV/metabolismo , Dolor Agudo/inducido químicamente , Dolor Agudo/metabolismo , Dolor Agudo/fisiopatología , Animales , Masculino , Ratones , Ratas , Xantófilas/farmacología

RESUMEN

Oil-in-water emulsions were prepared with carrot- or tomato-enriched olive oil (5%w/v) and stabilized with Tween80 or sucrose esters (0.5%w/v) with different hydrophilic-lipophilic balance (8; 11 or 16). All emulsions had similar initial oil droplet sizes and were submitted to simulated gastrointestinal conditions using a kinetic digestion procedure. Sucrose esters induced an unstable system after gastric conditions leading to coalesced oil droplets, while Tween80 emulsions remained stable. Emulsion particle sizes at the end of the gastric phase were directly associated with the lipolysis kinetics during the intestinal phase. Moreover, a direct relationship was observed between lipolysis and carotenoid micellarisation for all emulsions, and depended mainly on the surfactant structure used. Tween80 emulsions led to a higher lipolysis extent (53-57%) and carotenoid bioaccessibility (17-42%) compared to sucrose ester emulsions (33-52% and 9-27%, respectively). These findings show the importance of the emulsifier structure and emulsion stability during gastrointestinal conditions in modulating lipolysis kinetics.

Asunto(s)

Emulsionantes/química , Emulsiones/química , Lípidos/farmacocinética , Carotenoides/química , Carotenoides/farmacocinética , Daucus carota/química , Digestión , Emulsiones/metabolismo , Ésteres/química , Mucosa Gástrica/metabolismo , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Mucosa Intestinal/metabolismo , Cinética , Lípidos/química , Solanum lycopersicum/química , Aceite de Oliva/química , Tamaño de la Partícula , Polisorbatos/química , Tensoactivos/química

RESUMEN

Our current knowledge of the implications of endocannabinoids in fear and anxiety is largely based on fear conditioning paradigms and approach-avoidance conflicts. Here we establish the ethobehavioral beetle mania task (BMT), which confronts mice with an erratically moving robo-beetle. With the help of this task we demonstrate decreased tolerance yet increased avoidance responses to an approaching beetle in high-anxiety behavior (HAB) and BALBc mice compared to C57BL/6N, CD1 and normal-anxiety behavior (NAB) mice. Also DBA/2N mice showed decreased passive and increased active behavior, but followed the robo-beetle more often than HAB and BALBc mice. Treatment with diazepam (1 mg/kg) increased tolerance without affecting avoidance behavior in HAB mice. Treatment with the MAGL inhibitor JZL184 (8 mg/kg) increased flight behavior, but did not affect tolerance. The FAAH inhibitor URB597 (0.3 mg/kg), however, reduced flight behavior and enhanced tolerance to the robo-beetle. The latter effects were blocked by co-treatment with the CB1 receptor antagonist SR141716A (3 mg/kg), which failed to affect the behavior by itself. Taken together, we validate the BMT as a novel test for studying endocannabinoids beyond traditional paradigms and for assessing active fear responses in mice. Furthermore, we demonstrate panicolytic consequences of pharmacological enhancement of anandamide, but not 2-AG signaling.

Asunto(s)

Ansiedad/fisiopatología , Ácidos Araquidónicos/fisiología , Reacción de Prevención/fisiología , Conducta Animal/fisiología , Endocannabinoides/fisiología , Miedo/fisiología , Amidohidrolasas/antagonistas & inhibidores , Animales , Ansiolíticos/administración & dosificación , Reacción de Prevención/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Benzamidas/administración & dosificación , Benzodioxoles/administración & dosificación , Agonistas de Receptores de Cannabinoides/administración & dosificación , Carbamatos/administración & dosificación , Diazepam/administración & dosificación , Miedo/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Monoacilglicerol Lipasas/antagonistas & inhibidores , Piperidinas/administración & dosificación , Alcamidas Poliinsaturadas , Pirazoles/administración & dosificación , Receptor Cannabinoide CB1/antagonistas & inhibidores , Rimonabant

RESUMEN

Candesartan cilexetil is widely used in the management of hypertension and heart failure. The drug delivery encounters obstacles of poor aqueous solubility, efflux by intestinal P-glycoprotein and vulnerability to enzymatic degradation in small intestine. Self-nanoemulsifying drug delivery systems (SNEDDS) loaded with candesartan cilexetil were successfully developed to overcome such obstacles. Preliminary screening was carried out to select proper surfactant, co-surfactant and oil combination for successful SNEDDS formulation. All screened excipients were reported for their P-glycoprotein and cytochrome P450 3A4 (CYP3A4) modulation activity. Ternary and pseudo ternary diagrams were constructed to optimize the system. Peppermint oil and clove oil showed a high emulsification ability. The nature of obtained dispersions was identified to be nanoemulsions. Twenty-four formulations were evaluated for stability, robustness to dilution and self-emulsification efficiency. All formulations showed a very short emulsification time of <2min. The emulsification efficiency was significantly superior at pH6.8, at which the largest self-emulsifying region was also observed. Eight formulations were selected for further characterization according to cloud point measurement; mean droplet size, poly dispersity index (PDI) and zeta potential determination in addition to in vitro drug release study. All selected formulations showed very high cloud points (70-90°C), ultrafine mean droplet size (12±1.4 to 24.5±2.13nm), very low PDI values (0.015-0.1305) and almost a complete drug release after 12h. Formulation F15 (Peppermint oil 55% w/w: Cremophor RH40 25% w/w: Labrasol 20% w/w) was selected for further characterization. Its droplet size showed robustness to different dilution folds with different media and its TEM photograph showed spherical particles without any apparent aggregation even after 24h. Formulation F15 successfully controlled the systolic blood pressure of hypertensive rats for 24h with the maximum effect was observed after 2h. These results indicate that, SNEDDS could be promising delivery systems with a rapid onset of action and prolonged therapeutic effect of candesartan cilexetil.

Asunto(s)

Antihipertensivos/administración & dosificación , Bencimidazoles/administración & dosificación , Compuestos de Bifenilo/administración & dosificación , Sistemas de Liberación de Medicamentos , Hipertensión/tratamiento farmacológico , Tetrazoles/administración & dosificación , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Antihipertensivos/química , Bencimidazoles/química , Compuestos de Bifenilo/química , Citocromo P-450 CYP3A/metabolismo , Liberación de Fármacos , Emulsiones , Masculino , Aceites/administración & dosificación , Aceites/química , Ratas Wistar , Solubilidad , Tensoactivos/administración & dosificación , Tensoactivos/química , Tetrazoles/química

RESUMEN

Mono- and diacylglycerols rich in omega-3 have a great interest due to their good bioavailability and oxidation stability compared with other kind of omega-3 concentrates. The main drawback in mono- and diacylglycerols production by glycerolysis is the immiscibility of the substrates, oil and glycerol. To improve mass transfer rates, avoiding the use of organic solvents, emulsification of both reactants as reverse micelles (glycerol-in-oil) was carried out previous to lipase-catalyzed sardine oil glycerolysis. Substrate emulsification yielded higher reaction rates compared to kinetics with no previous emulsification, but still lower than in organic solvents. To avoid the use of organic solvent, SC-CO2 was used as reaction medium but no kinetic advantages were demonstrated in the pressure range from 15 to 25 MPa. By increasing temperature, from 40 to 90°C, reaction rates increased both in a solvent-free system and in SC-CO2 medium. It was also found that an increase in temperature does not lead to an increase in the final oxidation status of the reaction products. This behavior was due to the adsorption capacity of the Lipozyme 435 support, giving lower oxidation status at the highest temperature, 80-90°C.

Asunto(s)

Emulsiones , Aceites de Pescado , Glicerol , Lipasa , Dióxido de Carbono/química , Emulsiones/química , Emulsiones/metabolismo , Aceites de Pescado/química , Aceites de Pescado/metabolismo , Glicerol/química , Glicerol/metabolismo , Lipasa/química , Lipasa/metabolismo , Metabolismo de los Lípidos , Oxidación-Reducción , Presión , Temperatura

RESUMEN

Thermosensitive Chitosan hydrogels which can be injected into defects with minimally invasive approach were prepared. Also starch micro/nano particles were synthesized via water-in-oil (W/O) miniemulsion technique. The starch particles were incorporated into the chitosan hydrogel to prepare injectable thermosensitive hydrogel composites. Tube inverting method, compression tests, swelling studies, XRD, SEM, OM, DLS, UV-vis spectroscopy were used for investigations. Results revealed that increasing crosslinker and surfactant contents and stirring rate leads to particle size reduction. Particle size was modeled using design of experiments (DOE) via the response surface method (RSM). Due to analysis of variance (ANOVA), the particle sizes can be predicted by quadratic model within the design space. Gelation time and compressive modulus measurements showed the particles significant influence on the blend network density and hydrogel mechanical properties. Swelling measurements revealed that incorporation of starch particles in chitosan hydrogel increases its swelling coefficient significantly. The innovative architecture, namely micro/nano particles in gel can be considered as a dual delivery platform or smart scaffold for engineering of certain tissues.

RESUMEN

ETHOPHARMACOLOGICAL RELEVANCE: The Persea major (Meisn.) L.E. Kopp (Lauraceae) (botanical synonym: Persea pyrifolia (D. Don) Spreng, Persea pyrifolia Nees and Mart., Persea cordata var. major (Meisn.) Mez and Persea willdenovii Kosterm) is a medicinal plant native in the south of Brazil, where is popularly known as Pau de Andrade, Maçaranduba or Abacate-do-Mato. Its barks are commonly used to prepare an infusion which is administered orally or topically to treat ulcers and wounds, respectively. Thus, this study has been undertaken to contribute to the validation of the popular use of P. major to treat of ulcerative disorders from gastrointestinal system, using different experimental models in rodents. MATERIAL AND METHODS: Firstly, ultra-performance liquid chromatography coupled to a mass spectrophotometer has been performed. Next, the potential gastroprotective of hydroalcoholic extract of P. major barks (HEPM) (30-300mg/kg) has been evaluated in ulcer models acute as: ethanol, ethanol/HCl and indomethacin-induced ulcer. The extract (300mg/kg) has been also tested in acetic acid-induced chronic ulcer model. Histological, toxicological, histochemical, oxidative stress and gastric secretion parameters were analyzed. RESULTS: The main compounds found in HEPM were polyphenols as condensed tannins, flavonoids heterosides derivatives from quercetin and kaempferol. HEPM (300mg/kg, p.o) prevented gastric lesions induced by ethanol or indomethacin in rats by 58.98% and 97.48%, respectively, compared to vehicle group (148.00±14.83mm2 and 12.07±1.61mm2, respectively). In acetic acid-induced chronic ulcer model the HEPM (300mg/kg, p.o) reduced the ulcer are by 40.58%, compared to vehicle group (127.90±12.04mm2). The healing effect was confirmed histologically, by an increase in mucin content and by the reduction in oxidative and inflammatory parameters at the ulcer site. Neither significant effect on gastric acid secretion nor toxicological effects and cytotoxicity were provoked by administration of HEPM. CONCLUSIONS: The results allows to conclude that HEPM exerts gastroprotective and gastric cicatrizing effects favoring on protective defenses, but not possess antisecretory effect in contrast to the current antiulcer therapy, besides the extract present good tolerability and absence of cytotoxicity. Moreover, the results presented here contribute to the validation to the popular use of the P. major in the treatment of gastric ulcer.

Asunto(s)

Antiulcerosos/farmacología , Persea/química , Extractos Vegetales/farmacología , Úlcera Gástrica/tratamiento farmacológico , Animales , Antiulcerosos/química , Masculino , Fitoquímicos , Fitoterapia , Extractos Vegetales/química , Plantas Medicinales , Factores Protectores , Ratas

RESUMEN

Commonly used hypnotics have undesirable side-effects, especially during continuous usage. On the other hand, some herbal products, which are used for prolonged periods, are suggested to have a sleep inducing property, though the claims have not been validated scientifically. The hypnotic potential of α-Asarone, an active principle of Acorus species, was tested in the present study by first identifying the optimal dose of α-Asarone for improving sleep, followed by studies that evaluated the effect of repeated administration of this optimal dose for five days on sleep deprived rats. Of all the doses tested (2, 10, 40, 80 and 120 mg/kg), 10 mg/kg α-Asarone improved the quality of sleep, as indicated by an increased NREM bout duration, reduced arousal index, and decreased bout frequencies of NREM sleep and wakefulness. A marginal decrease in the hypothalamic and body temperatures was also observed. Higher doses, on the other hand, not only reduced the quantity and quality of sleep, but also produced hypothermia. In sleep deprived rats, administration of 10 mg/kg α-Asarone for five consecutive days improved the quality of sleep in contrast to the vehicle and a known hypnotic midazolam. Improvement in NREM sleep quality was observed when the difference between the hypothalamic and the body temperature was minimum. An enhanced association between NREM sleep bout duration and hypothalamic temperature was also observed after administration of 10 mg/kg α-Asarone. This comprehensive study is the first report on the hypnotic property of α-Asarone, which validates its potential to be considered for treatment of insomnia.

Asunto(s)

Anisoles/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Sueño/efectos de los fármacos , Derivados de Alilbenceno , Animales , Anisoles/efectos adversos , Temperatura Corporal/efectos de los fármacos , Temperatura Corporal/fisiología , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Relación Dosis-Respuesta a Droga , Electrodos Implantados , Electroencefalografía , Hipnóticos y Sedantes/efectos adversos , Hipotermia/inducido químicamente , Hipotermia/fisiopatología , Masculino , Midazolam/farmacología , Modelos Animales , Ratas Wistar , Sueño/fisiología , Privación de Sueño/tratamiento farmacológico , Privación de Sueño/fisiopatología , Vigilia/efectos de los fármacos , Vigilia/fisiología

RESUMEN

Dimethyl fumarate (DMF) is an orally administered drug with neuroprotective and immunomodulatory activities. It has potential uses in the treatment of neurodegenerative diseases such as Alzheimer's disease (AD). The objective of this study was to investigate the feasibility of transdermal delivery of DMF by studying the effect of different penetration enhancers on the skin permeation of DMF. The permeation of saturated DMF solutions was investigated in propylene glycol (PG) with varying concentrations of each of the following enhancers: Polysorbate 80 (T80), N-methyl pyrrolidone (NMP), laurocapram (Azone®) (Az), Transcutol P (Tc), Terpineol (Terp), and cineole (Cin) using vertical Franz diffusion cells and human cadaver skin. The results showed that all penetration enhancers improved the rate of permeation of DMF. The rank order for the highest concentration of each enhancer was as follows: Cin > Az>TC > Terp>T80≥NMP. The most effective penetration enhancer was shown to be 5% cineole with a 5.3-fold increase in the enhancement ratio (ER). The amounts of drug delivered suggest that DMF is a potential candidate for transdermal drug delivery.

Asunto(s)

Enfermedad de Alzheimer/tratamiento farmacológico , Dimetilfumarato/administración & dosificación , Sistemas de Liberación de Medicamentos , Absorción Cutánea , Administración Cutánea , Humanos , Piel

RESUMEN

Coptisine is one of the main constituents of Coptis chinensis which has been widely used for the remedy of inflammatory disorders. Although the biological activities of coptisine have been well known, the pharmacological properties of its free base have seldomly been elucidated thus far. The aim of this study was to investigate the potential anti-inflammatory properties of coptisine free base (CFB, 8-hydroxy-7,8-dihydrocoptisine) on three animal models, namely xylene-induced ear edema, acetic acid-induced vascular permeability and carrageenan-induced paw edema. The results exhibited that CFB exerted a dose-dependent suppression on ear edema induced by xylene, significantly mitigated the aggravation of vascular permeability caused by acetic acid and paw edema induced by carrageenan. Additionally, CFB significantly suppressed the productions of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), prostaglandinE2 (PGE2) and tumor necrosis factor (TNF-α) in the drug-treated groups as compared with the vehicle group after treatment with carrageenan. Signaling events of nuclear factor-κB (NF-κB) translocation, such as p-IKKα, p-IKKß, p-IκBα and p65 (nucleus) were significantly inactivated, while inhibitor of nuclear factor κBα (IκBα) and p65 (cytosolic) were markedly up-regulated by CFB. Furthermore, CFB also significantly suppressed the mitogen-activated protein kinase (MAPK) pathway by blocking the phosphorylation of p-p38 (phospho-p38 mitogen-activated protein kinases) and p-JNK (phospho-c-jun N-terminal kinase) but not p-ERK (phospho-extracellular signal-regulated kinase). Hence, CFB efficiently prevented inflammation, at least partially, via inhibition of NF-κB and MAPK pathways. These findings provided a pioneering pharmacological basis for the anti-inflammatory effect of CFB and suggested CFB might be a potential candidate for the therapy of inflammatory disorders.

Asunto(s)

Antiinflamatorios/farmacología , Berberina/análogos & derivados , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , FN-kappa B/metabolismo , Ácido Acético/farmacología , Animales , Antiinflamatorios/uso terapéutico , Berberina/farmacología , Berberina/uso terapéutico , Permeabilidad Capilar/efectos de los fármacos , Dinoprostona/metabolismo , Relación Dosis-Respuesta a Droga , Edema/tratamiento farmacológico , Edema/metabolismo , Edema/patología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Ratones , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Glycyrrhiza polysaccharide liposome (GPSL) was prepared by reverse-phase evaporation method and optimized with response surface methodology. As a result, the optimum preparation conditions were as follows: the ratio of soybean phosphatide to Glycyrrhiza polysaccharide (GPS) of 24:1, temperature of drug incubation of 46°C, the ultrasound time of 16min. Confirmation experiments and transmission electron micrograph (SEM) exhibited the entrapment efficiency of liposome as 78.33±0.25%, with spherical shape and uniform sizes. Furthermore, proliferation assay, allogeneic mixed lymphocyte reaction and supernatant cytokines of chBM-DCs were performed by MTT and ELISA methods to investigate the immune-modulating effects of GPSL and GPS. The results showed that GPSL could significantly promote the proliferation of immature chBM-DCs, enhance the ability of mature chBM-DCs to induce T-cell proliferation and modulate the mature chBM-DCs to secret cytokines such as IL-2, IFN-γ and IL-10. These evidences indicated that the immune-modulating activity of GPS was significantly improved after encapsulated with liposome.

Asunto(s)

Glycyrrhiza/química , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/farmacología , Polisacáridos/administración & dosificación , Polisacáridos/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Pollos , Citocinas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Liposomas , Masculino , Modelos Teóricos , Linfocitos T/citología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Temperatura , Ondas Ultrasónicas

RESUMEN

Direct introduction of essential oils (EOs) into biopolymer-based packaging materials faces various challenges such as insolubility and loss of activity. The aim of this study was increasing the bioactivity of Zataria multiflora essential oil (ZMEO) through first making a nanoemulsion and then immobilizing within basil seed gum (BSG)-based film network. ZMEO (nano)emulsions were prepared using high intensity ultrasound approach at 150W and various sonication times (0, 2.5, 5 and 10min). An increase in the antibacterial activity of ZMEO nanoemulsion was observed by decreasing the nanoemulsion droplet size. Increasing nanoemulsion concentration in BSG film matrix improved the mechanical properties. Scanning electron micrographs showed that the presence of ZMEO nanoemulsions resulted in significant changes in the microstructure of BSG films. Antimicrobial films were effective against potential foodborne pathogens. This innovative incorporation of EOs into biopolymer-based films may have implications in extending the shelf life of food products through retarding the release of volatile constituents.

Asunto(s)

Embalaje de Alimentos , Lamiaceae/química , Ocimum basilicum/química , Aceites Volátiles/química , Gomas de Plantas/química , Semillas/química , Emulsiones , Contaminación de Alimentos/prevención & control , Nanoestructuras

RESUMEN

Many lead compounds have a low solubility in water, which substantially hinders their clinical application. Nanosuspensions have been considered a promising strategy for the delivery of water-insoluble drugs. Here, denatured soy protein isolate (SPI)-coated docetaxel nanosuspensions (DTX-NS) were developed using an anti-solvent precipitation-ultrasonication method to improve the water-solubility of DTX, thus improving its intracellular delivery. DTX-NS, with a diameter of 150-250nm and drug-loading up to 18.18%, were successfully prepared by coating drug particles with SPI. Interestingly, the drug state of DTX-NS was alterable. Amorphous drug nanoparticles were obtained at low drug-loading, whereas at a high drug-loading, the DTX-NS drug was mainly present in the crystalline state. Moreover, DTX-NS could be internalized at high levels by cancer cells and enter the cytosol by lysosomal escape, enhancing cell cytotoxicity and apoptosis compared with free DTX. Taken together, denatured SPI has a strong stabilization effect on nanosuspensions, and the drug state in SPI-coated nanosuspensions is alterable by changing the drug-loading. Moreover, DTX-NS could achieve cytosolic delivery, generating enhanced cell cytotoxicity against cancer cells.

Asunto(s)

Antineoplásicos , Citosol/metabolismo , Portadores de Fármacos , Nanopartículas , Proteínas de Soja , Taxoides , Células A549 , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Docetaxel , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Liberación de Fármacos , Estabilidad de Medicamentos , Humanos , Interferón-alfa/sangre , Interleucina-12/sangre , Ratones Endogámicos ICR , Nanopartículas/administración & dosificación , Nanopartículas/química , Desnaturalización Proteica , Suero/química , Proteínas de Soja/administración & dosificación , Proteínas de Soja/química , Proteínas de Soja/farmacología , Taxoides/administración & dosificación , Taxoides/química , Taxoides/farmacología

RESUMEN

The aim of this research was to prepare of bionanocomposite films based on chitosan (CH) incorporated with Carum copticum essential oil and reinforced with cellulose nanofibers (CNF) or lignocellulose nanofibers (LCNF). The FTIR analysis showed new interactions in bionanocomposites. AFM and SEM analyses showed an increased roughness for bionanocomposites but suggested good dispersion of CNF and LCNF in CH matrix. X-ray diffraction confirmed that the degree of crystallinity was increased by addition of CNF/LCNF. The results suggested that the CH-EO film had high antioxidant activity and was more effective against E. coli and B. cereus bacteria than CH-EOCNF and CH-EO-LCNF films, which shows the release controlling effect of nanofibers. Mechanical properties were improved with addition of EO and CNF/LCNF. Incorporation of EO and CNF/LCNF improved water vapor barrier properties of films. In general, uniform dispersion and improving effect of LCNF on properties of CH-EO films was more than CNF.

Asunto(s)

Carum/química , Quitosano , Nanofibras , Aceites Volátiles/química , Aceites de Plantas/química , Bacillus cereus , Escherichia coli , Embalaje de Alimentos