RESUMEN
Glycyrrhiza glabra extract is widely known for its antioxidant and anti-inflammatory properties and can improve the wound healing process. The aim of this work was to shorten the time of the healing process by using an eco-sustainable wound dressing based on Spanish broom flexible cellulosic fabric by impregnation with G. glabra extract-loaded ethosomes. Chemical analysis of G. glabra extract was performed by LC-DAD-MS/MS and its encapsulation into ethosomes was obtained using the ethanol injection method. Lipid vesicles were characterized in terms of size, polydispersity index, entrapment efficiency, zeta potential, and stability. In vitro release studies, biocompatibility, and scratch test on 3T3 fibroblasts were performed. Moreover, the structure of Spanish broom dressing and its ability to absorb wound exudate was characterized by Synchrotron X-ray phase contrast microtomography (SR-PCmicroCT). Ethosomes showed a good entrapment efficiency, nanometric size, good stability over time and a slow release of polyphenols compared to the free extract, and were not cytotoxic. Lastly, the results revealed that Spanish broom wound dressing loaded with G. glabra ethosomes is able to accelerate wound closure by reducing wound healing time. To sum up, Spanish broom wound dressing could be a potential new green tool for biomedical applications.
Asunto(s)
Vendajes , Celulosa , Glycyrrhiza , Extractos Vegetales , Spartium , Cicatrización de Heridas , Animales , Ratones , Glycyrrhiza/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Cicatrización de Heridas/efectos de los fármacos , Celulosa/química , Celulosa/farmacología , Spartium/química , Células 3T3RESUMEN
New-generation antidepressants are a heterogeneous class of drugs used in the treatment of depression and related disorders. This review deals with the first new-generation antidepressant class to enter the pharmaceutical market, i.e., selective serotonin reuptake inhibitors (SSRIs), which are still the most prescribed and widely used ones. Their common characteristics are the comparable clinical efficacy, good tolerability and relative safety in comparison to "first generation antidepressants", i.e. classic tricyclic antidepressants and monoamine oxidase inhibitors. This class of drugs includes fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine and, since 2011, vilazodone. In this review, the main pharmacodynamic and pharmacokinetic properties of the six commercially available SSRIs are described, focusing on side and toxic effects, chemical-clinical correlations, interactions with other drugs, the role of therapeutic drug monitoring (TDM) and related bioanalytical methodologies.
Asunto(s)
Trastorno Depresivo/tratamiento farmacológico , Monitoreo de Drogas , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Benzofuranos/efectos adversos , Benzofuranos/farmacocinética , Benzofuranos/uso terapéutico , Citalopram/efectos adversos , Citalopram/farmacocinética , Citalopram/uso terapéutico , Trastorno Depresivo/metabolismo , Fluoxetina/efectos adversos , Fluoxetina/farmacocinética , Fluoxetina/uso terapéutico , Fluvoxamina/efectos adversos , Fluvoxamina/farmacocinética , Fluvoxamina/uso terapéutico , Humanos , Indoles/efectos adversos , Indoles/farmacocinética , Indoles/uso terapéutico , Paroxetina/efectos adversos , Paroxetina/farmacocinética , Paroxetina/uso terapéutico , Piperazinas/efectos adversos , Piperazinas/farmacocinética , Piperazinas/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacocinética , Sertralina/efectos adversos , Sertralina/farmacocinética , Sertralina/uso terapéutico , Clorhidrato de VilazodonaRESUMEN
We used Flinder Sensitive Line (FSL) rats, a genetic model of unipolar depression, to examine whether changes in central GABAergic transmission are associated with a depressed phenotype. FSL rats showed an increased behavioral response to low doses of diazepam, as compared to either Sprague Dawley (SD) or Flinder Resistant Line (FRL) rats used as controls. Diazepam at a dose of 0.3 mg/kg, i.p., induced a robust impairment of motor coordination in FSL rats, but was virtually inactive in SD or FRL rats. The increased responsiveness of FSL rats was not due to changes in the brain levels of diazepam or its active metabolites, or to increases in the number or affinity of benzodiazepine recognition sites, as shown by the analysis of [(3)H]-flunitrazepam binding in the hippocampus, cerebral cortex or cerebellum. We therefore examined whether FSL rats differed from control rats for the expression levels of the K(+)/Cl(-) cotransporter, KCC2, which transports Cl(-) ions out of neurons, thus creating the concentration gradient that allows Cl(-) influx through the anion channel associated with GABA(A) receptors. Combined immunoblot and immunohistochemical data showed a widespread increase in KCC2 expression in FSL rats, as compared with control rats. The increase was more prominent in the cerebellum, where KCC2 was largely expressed in the granular layer. These data raise the interesting possibility that a spontaneous depressive state in animals is associated with an amplified GABAergic transmission in the CNS resulting from an enhanced expression of KCC2.
Asunto(s)
Cerebelo/metabolismo , Corteza Cerebral/metabolismo , Trastorno Depresivo/metabolismo , Hipocampo/metabolismo , Simportadores/metabolismo , Animales , Fármacos del Sistema Nervioso Central/administración & dosificación , Fármacos del Sistema Nervioso Central/farmacocinética , Fármacos del Sistema Nervioso Central/farmacología , Cerebelo/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Diazepam/administración & dosificación , Diazepam/farmacocinética , Diazepam/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hipocampo/efectos de los fármacos , Masculino , Destreza Motora/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores de GABA-A/metabolismo , Especificidad de la Especie , Cotransportadores de K ClRESUMEN
A sensitive high-performance liquid chromatographic method has been developed for the determination of homovanillic acid (HVA), the main metabolite of dopamine, in human plasma. Analyses were carried out on a reversed-phase column (C8, 250 mm x 4.6 mm i.d., 5 microm) using a mobile phase composed of 10% methanol and 90% aqueous citrate buffer, containing octanesulfonic acid and EDTA at pH 4.8. Coulometric detection was used, setting the guard cell at +0.100 V, the first analytical cell at -0.200 V and the second analytical cell at +0.500 V. A careful solid-phase extraction procedure, based on strong anion exchange (SAX) cartridges (100 mg, 1 mL), was implemented for the pre-treatment of plasma samples. Extraction yield was satisfactory, being the mean value 98.0%. The calibration curve was linear over the concentration range of 0.2-25.0 ng mL(-1) of homovanillic acid. The limit of quantitation (LOQ) was 0.2 ng mL(-1) and the limit of detection (LOD) was 0.1 ng mL(-1). The method was successfully applied to plasma samples from former alcohol, cocaine and heroin addicts. Results were satisfactory in terms of precision and accuracy. Hence, the method is suitable for the determination of homovanillic acid in human plasma.