Enhanced antitumor activity of doxorubicin in breast cancer through the use of poly(butylcyanoacrylate) nanoparticles.

The use of doxorubicin (DOX), one of the most effective antitumor molecules in the treatment of metastatic breast cancer, is limited by its low tumor selectivity and its severe side effects. Colloidal carriers based on biodegradable poly(butylcyanoacrylate) nanoparticles (PBCA NPs) may enhance DOX antitumor activity against breast cancer cells, thus allowing a reduction of the effective dose required for antitumor activity and consequently the level of associated toxicity. DOX loading onto PBCA NPs was investigated in this work via both drug entrapment and surface adsorption. Cytotoxicity assays with DOX-loaded NPs were performed in vitro using breast tumor cell lines (MCF-7 human and E0771 mouse cancer cells), and in vivo evaluating antitumor activity in immunocompetent C57BL/6 mice. The entrapment method yielded greater drug loading values and a controlled drug release profile. Neither in vitro nor in vivo cytotoxicity was observed for blank NPs. The 50% inhibitory concentration (IC50) of DOX-loaded PBCA NPs was significantly lower for MCF-7 and E0771 cancer cells (4 and 15 times, respectively) compared with free DOX. Furthermore, DOX-loaded PBCA NPs produced a tumor growth inhibition that was 40% greater than that observed with free DOX, thus reducing DOX toxicity during treatment. These results suggest that DOX-loaded PBCA NPs have great potential for improving the efficacy of DOX therapy against advanced breast cancers.

Análisis de sistemas bucoadhesivos / Analysis of bucoadhesive systems

Objetivo: El objetivo de este estudio es el diseño de un parche bucoadhesivo para la administración transbucal de clorhidrato de doxepina utilizando diferentes polímeros así como la caracterización de dichos sistemas en cuanto al análisis calorimétrico y la capacidad de hinchamiento. Materiales y métodos: Se ha utilizado clorhidrato de doxepina y diferentes polímeros, carboximetilcelulosa sódica, hidroxipropilmetilcelulosa y chitosan. La calorimetría diferencial de barrido (DSC) se ha realizado en un dispositivo Mettler FP 80 equipado con un horno FP 85 y la capacidad de hinchamiento utilizando placas de agar. Resultados: Se obtienen termogramas de los parches y las mezclas físicas donde se observan transiciones endotérmicas entre 30 y 120º C y el pico endotérmico del principio activo en las mezclas físicas binarias. La entalpía de deshidratación es similar en los polímeros de carboximetilcelulosa sódica y chitosan (281 J/g) siendo menor en la película de hidroxipropilmetilcelulosa (251 J/g), al igual que el porcentaje de hidratación donde se demuestra que los parches elaborados con hidroxipropilmetilcelulosa presenta menor tendencia a captar agua (55,91 %) frente al 67,04 % y 67,30 % de la carboximetilcelulosa sódica y chitosan, respectivamente. Conclusión: Los resultados obtenidos muestran que existe compatibilidad entre los componentes de la formulación y los datos de entalpía se correlacionan con los datos obtenidos en el ensayo de hinchamiento (AU)

Aim: The aim of this study is to design a bucoadhesive patch for the transbuccal administration of doxepin hydrochloride using different polymers as well as the characterization of these systems for calorimetric analysis and the swelling capacity. Materials and methods: Doxepin hydrochloride was used as well as various polymers; carboxymethylcellulose sodium, hydroxypropylmethyl cellulose and chitosan. Differential scanning calorimetry (DSC) was carried out using a Mettler FP 80 device equipped with a FP 85 oven and the swelling capacity using agar plates. Results: Thermograms obtained patches and physical mixtures where there are endothermic transitions between 30 and 120º C and the endothermic peak of the active principle in binary physical mixtures. Dehydration enthalpy is similar in polymers of carboxymethylcellulose sodium and chitosan (281 J/g), the film having less hydroxypropylmethylcellulose (251 J/g), the percentage of moisture shows that the patches prepared with hydroxypropylmethylcellulose have less tendency to collect water (55.91 %) compared to 67.04 % and 67.30 % with sodium carboxymethylcellulose and chitosan, respectively. Conclusion: The results show that there is compatibility between the components of the formulation and the enthalpy data correlate with the data obtained in the swelling test (AU)

Vaginistis: Etiología, diagnóstico y profilasis / No disponible

La vaginitis es uno de los problemas ginecológicos más frecuentes, diagnosticado por los médicos de atención primaria. En este artículo hemos querido recoger los diferentes tipos de vaginitis, así como la sintomatología que los caracteriza y los posibles tratamientos farmacológicos. Sin embargo, la presencia de episodios recurrentes y la aparición de reacciones adversas por la reexposición a antibióticos ponen de manifiesto la necesidad de una alternativa terapéutica. Numerosos estudios sugieren la utilización de probióticos para el tratamiento de esta patología basándose en la capacidad reguladora que estos tienen sobre la microbiota vaginal, y que se caracterizada por la habilidad que tienen para mantener un pH vaginal menor igual 4,5, la producción de biosurfactantes y el bloqueo de la adhesión de los uropatogenos. El hecho de que la colonización del tracto genitourinario sea más rápida al administrar los probióticos por vía vaginal que por vía oral sugiere que la administración de estos por dicha vía podría ser muy ventajosa(AU)

Vaginitis is one of the most common gynecological problems diagnosed by primary care physicians. In this article we wanted to describe the different types of vaginitis, their symptoms and the different drug treatments. The presence of recurrent episodes and the re-exposure to antibiotics can cause adverse reactions and suggesting the need for alternative treatment. Numerous studies propose the use of probiotics for the treatment of this pathology basing on the regulatory capacity that probiotics have on the vaginal microbiota. This capacity is due to the ability to maintain vaginal pH =< 4.5, the production of biosurfactants and blocking adhesion of uropathogens. The fact that the colonization of the genitourinary tract is faster when probiotics are administered vaginally suggesting that this kind of administration could have a lot of advantages(AU)

Potenciación de la actividad antitumoral de doxorrubicina mediante su formulación en nanoplataformas magnéticas / Improvement of the antitumor activity of doxorubicin by the use of magnetic nanoplatforms

El diseño de sistemas transportadores basados en nanopartículas magnéticas pretende la acumulación en el tejido tumoral de la dosis de fármaco administrada. Así debe obtenerse una mejora significativa del efecto anticanceroso, junto con la minimización de la toxicidad asociada. En este contexto, desarrollamos una metodología reproducible de formulación de nanopartículas constituidas por núcleos de óxido de hierro (magnetita) embebidos en una matriz de poli (E- caprolactona). La extensa caracterización fisicoquímica de estos nanocompuestos permitió definir las condiciones óptimas de formulación para asegurar el transporte eficaz de fármacos. Se estudió la capacidad de la nanoplataforma para desarrollar un efecto antitumoral de hipertermia, su compatibilidad sanguínea y su utilización por vía intravenosa como sistema transportador de doxorrubicina hasta el tejido canceroso. Las nanopartículas magnetita/pol i(E-caprolactona) presentaron una adecuada vehiculización de este fármaco, junto con una muy significativa susceptibilidad magnética. Finalmente, se analizó la actividad antitumoral de los nanocompuestos cargados con doxorrubicina en un modelo de tumor subcutáneo EMT6 inducido en ratones. Se observó que éstos presentaban un marcado efecto quimioterápico en comparación con tratamientos alternativos (p.ej., la administración de estas nanopartículas sin guiado magnético hasta la masa tumoral, o el tratamiento con una solución intravenosa de doxorrubicina). Los resultados obtenidos resaltan las interesantes propiedades que presenta la nanoformulación diseñada para el desarrollo de una terapia eficaz contra el cáncer(AU)

The introduction of magnetic nanoplatforms in the cancer arena is intended to optimize the accumulation of the drug dose into the tumor interstitium with the help of a magnetic gradient. As a result, the chemotherapeutic agent may exhibit an enhanced anticancer efficacy and a negligible systemic toxicity. In these contexts, we have developed a reproducible methodology for the design of magnetite/poly (E-caprolactone) core/shell nanoparticles. A detailed physicochemical characterization of these nanocomposites suggested that their heterogeneous structure allows their use in drug delivery, thanks to an excellent responsiveness to magnetic gradients. In vitro heating characteristics (hyperthermia inducing capability) of the core/shell nanoparticles were investigated in a high frequency alternating magnetic gradient. Blood compatibility of the nanoformulation was defined in vitro. Finally, this nanodevice was used to enhance the intravenous delivery of the anticancer agent doxorubicin to the tumor tissue. The nanocomposites were characterized by an adequate doxorubicin loading, a significant magnetic susceptibility, and a low burst drug release. When injected to the EMT6 subcutaneous mice tumor model, these doxorubicin-loaded core/shell nanoparticles were magnetically guided, and they displayed considerably greater anticancer activity than the other anticancer treatments (i.e., doxorubicin-loaded nanocomposites non-magnetically guided, or doxorubicin free in solution). Thus, the here-described stimuli-sensitive nanomedicine possesses important characteristics for effective therapy of cancer(AU)

Delivery systems for natural antioxidant compounds: Archaeosomes and archaeosomal hydrogels characterization and release study.

The aim of this study was to use archaeosomes, a novel kind of liposomes made up by archaeal polar lipids, both multilamellars (MLVs) and unilamellars (SUVs), as a topical delivery system for natural antioxidant compounds recovered from olive mill waste. For comparative purpose an analogue formulation of phosphatidylcholine liposomes was prepared. SUVs were smaller than MLVs ones, showing size values smaller than 200nm, which was maintained during the stability study. Transmission electron microscopy showed spherical morphology for conventional liposomes while archaeosomes had more irregular membranes. Vesicle encapsulation efficiency was quite similar in both formulations and was enough to ensure a good antioxidant activity. Stability studies were performed one month after the preparation of formulations, which showed a high stability with no change in the initial characteristics of the suspensions. Furthermore, the possibility of incorporating the liposomal suspensions in different excipients (Carbopol-940(®) and Pluronic-127(®)) for topical administration was studied. In order to evaluate the release behaviour of the different systems prepared, in vitro diffusion studies were carried out using vertical diffusion Franz cells. In both cases the incorporation of the vesicles into the gels lead in a sustained release for 24h. Archaeosome gels released a similar amount of phenolic compounds regardless the excipient used, while in liposomal gels great release differences were found between carbopol and pluronic gel.

Rheological behavior of gels and meloxicam release.

The aim of this work was to identify a gel with suitable organoleptic and rheological properties (spreadability, texture and viscosity) for topical administration, designed to allow fast release of the active principle. The release of Meloxicam (anti-inflammatory agent) from olive oil lipogels was compared with a Carbopol hydrophilic prepared gel. In order to improve the diffusion of the active principle, two different artificial membranes with different pore size were used, before release assays in diffusion cells were compared. Drug released rate were obtained by Higuchi's model. Release rate and rheological properties relations were studied, and the best results were obtained for the gel prepared with an olive oil emulgent (Olivem 900).