Biological Implications of a Stroke Therapy Based in Neuroglobin Hyaluronate Nanoparticles. Neuroprotective Role and Molecular Bases.

Exogenous neuroprotective protein neuroglobin (Ngb) cannot cross the blood-brain barrier. To overcome this difficulty, we synthesized hyaluronate nanoparticles (NPs), able to deliver Ngb into the brain in an animal model of stroke (MCAO). These NPs effectively reached neurons, and were microscopically identified after 24 h of reperfusion. Compared to MCAO non-treated animals, those treated with Ngb-NPs showed survival rates up to 50% higher, and better neurological scores. Tissue damage improved with the treatment, but no changes in the infarct volume or in the oxidative/nitrosative values were detected. A proteomics approach (p-value < 0.02; fold change = 0.05) in the infarcted areas showed a total of 219 proteins that significantly changed their expression after stroke and treatment with Ngb-NPs. Of special interest, are proteins such as FBXO7 and NTRK2, which were downexpressed in stroke, but overexpressed after treatment with Ngb-NPs; and ATX2L, which was overexpressed only under the effect of Ngb. Interestingly, the proteins affected by the treatment with Ngb were involved in mitochondrial function and cell death, endocytosis, protein metabolism, cytoskeletal remodeling, or synaptic function, and in regenerative processes, such as dendritogenesis, neuritogenesis, or sinaptogenesis. Consequently, our pharmaceutical preparation may open new therapeutic scopes for stroke and possibly for other neurodegenerative pathologies.

Hyaluronate Nanoparticles as a Delivery System to Carry Neuroglobin to the Brain after Stroke.

Therapies against stroke can restore the blood supply but cannot prevent the ischemic damage nor stimulate the recovery of the infarcted zone. The neuroglobin protein plays an important role in the neuro-regeneration process after stroke; however, the method for its effective systemic application has not been identified yet, as neuroglobin is unable to pass through the blood-brain barrier. Previously, we developed different types of sodium hyaluronate nanoparticles, which successfully cross the blood-brain barrier after stroke. In this work, these nanoparticles have been used to carry neuroglobin through the bloodstream to the nerve cells in rats submitted to stroke. We have biosynthesized rat-recombinant neuroglobin and determined the formulation of sodium hyaluronate nanoparticles loaded with neuroglobin, as well as its size and ζ-potential, encapsulation efficiently, in vitro release, and its kinetic of liberation. The results show that the formulation achieved is highly compatible with pharmaceutical use and may act as a delivery system to transport neuroglobin within the blood. We have found that this formulation injected intravenously immediately after stroke reached the damaged cerebral parenchyma at early stages (2 h). Neuroglobin colocalizes with its nanocarriers inside the nerve cells and remains after 24 h of reperfusion. In conclusion, the systemic administration of neuroglobin linked to nanoparticles is a potential neuroprotective drug-delivery strategy after stroke episodes.

A novel double-layer mucoadhesive tablet containing probiotic strain for vaginal administration: Design, development and technological evaluation.

Vulvovaginal candidosis caused by Candida spp. is the most prevalent vaginal infection in Europe and the second one in EE.UU, so it has become a major female concern. Probiotics bacteria have been proposed as an alternative treatment with the aim of avoiding the adverse effects associated with conventional therapies including antibiotics and other aggressive drugs for the vaginal mucosa and microbiota. The purpose of this work was to design and develop a novel vaginal tablet that contained Lactobacillus spp. bacteria as a treatment against vulvovaginal infections. A total of 21 two-layers vaginal tablets, which contained different polymeric ratios, were proposed. However, formulation F4 (20mg Na-CMC; 50mg Carbopol® 934; 20mg chitosan) was selected as optimal according to its swelling index and dissolution/erosion capability. F4 tablets showed suitable technological properties for vaginal administration as well as mucoadhesion time (24.36±0.88h) and force (0.0941N). Disintegration assay in simulated vaginal fluid (SVF, pH5.5) showed that effervescent layer disappeared in 27.48±0.05s whilst matrix layer was totally gelled in 1h. Two different release profiles were achieved; on the one hand, a promptly release due to the dissolution of both effervescent layer and matrix layer's surface (1.10×108CFU/g), on the second hand, a prolonged released of the remaining bacteria until 24h (5.48×107CFU/g). For stability and storage study, it was found that bacteria viability was constant until 90days in both ways of storage, in a desiccator and at room temperature, with a final dosage of 108CFU/g which was considered appropriate for vaginal therapy (108-1010CFU/g).

Estudio bibliometrico sobre el impacto de los medicamentos biosimilares / Bibliometric Study About the Impact of Biosimilars Drugs

Objetivos: La bibliometría es un tipo de estudio estadístico sobre datos científicos. Mediante esta herramienta queremos valernos para visualizar distintos aspectos que presentan los medicamentos biosimilares, su importancia y el impacto que generan en su entorno. Métodos: se ha utilizando como motor de búsqueda Science Direct, así como de publicaciones científicas referenciadas en la bibliografía y como de algunas webs sobre la materia. Resultados: Casi todos los indicadores señalan la gran importancia económica que concierne entorno a los medicamentos biosimilares, la actualidad que presenta y que gran parte de su estudio se concentra alrededor de los pacientes. Conclusiones: Con este trabajo se comprueba el gran interés que ofrecen los biosimilares y sobre todo el impacto que tendrán en un futuro, así como las repercusiones que traerán consigo, sobre todo en los campos económicos y de la salud

Objectives: A bibliometrics study is a type of statistical study on scientific data. With this tool we want to visualize different aspects of biosimilar drugs, their importance and the impact they generate in their environment. Methods: Science Direct was utilized as a search engine, in addition to the scientific publications referenced in the bibliography as well as some websites concerning the subject. Results: Almost all the indicators point to the great economic importance of biosimilar drugs, their novelty and their patient-coentered focus. Conclusions: It is of great interest to know the future impact that these medicines will have and the repercussions they will bring, especially in the economic and health fields

Microorganismos probióticos y salud / Probiotic microorganisms and health

Objetivo: Mostrar los beneficios de los microorganismos probióticos sobre la salud y su aceptación por parte del consumidor, así como hacer una recopilación de todos los productos probióticos disponibles en el mercado farmacéutico. Material y métodos: Se realizó un estudio del mercado farmacéutico en relación a las formas farmacéuticas con microorganismos probióticos existentes y su evolución en los últimos años. La clasificación de todos los productos probióticos se llevó a cabo en función de la forma farmacéutica en la que se presentan;cada producto irá acompañado de la dosis de microorganismos probióticos que contiene, expresada como Unidades Formadoras de Colonias (UFC). Resultados: Es cada vez mayor el número de cepas probióticas aisladas y los beneficios mostrados sobre la salud del hombre. Encontramos gran diversidad de productos probióticos disponibles en oficinas de farmacia como consecuencia de una demanda cada vez mayor por parte del consumidor; no obstante, cabe resaltar el hecho de que muchos de ellos carecen en envase de información necesaria, por ejemplo, la dosis contenida. Conclusiones: El interés por parte de la industria farmacéutica en lazar nuevas formas farmacéuticas contenidas en microorganismos probióticos será cada vez mayor e irá ligado a la necesidad de una reglamentación específica para estos productos. Muchos de ellos no contienen la dosis mínima requerida para obtener un efecto beneficioso en la salud lo que supone una publicidad engañosa para el consumidor, por tanto, deberían ser retirados del mercado, publicitando únicamente aquellos que contengan una dosis terapéutica y cuyos efectos estén avalados por diferentes ensayos clínicos (AU)

Aims: Show the benefits of the probiotic microorganisms on health and its acceptance by the consumer. As well as collect those probiotic products available in pharmaceutical market. Materials and methods: A study of the pharmaceutical marketin relation to the existing dosage forms with probiotic microorganisms and their evolution in recent years was made. Classifying probiotic products was conducted according to the dosage form in which they are presented; each product must be accompanied by the dose of probiotic-containing, expressed as Colony Forming Units(CFU). Results: It is increasing the number of probiotic strains isolated and the benefits that its shown on human health. We found a diversity of probiotic products available in pharmacies as a result of an increasing demand by consumers; it is important to note that many of them lack necessary information on packaging, for example, the dose contained. Conclusions: The interest of the pharmaceutical industry in develop new dosage forms contained in probiotic microorganisms will be growing and will be linked to the need for a specific regulation for these products. Many of them do not contain the required dose to obtain a beneficial effect on health which is misleading advertising to consumers, therefore, they should be removed from the market, advertising only those products which contain a therapeutic dose and whose effects are endorsed by various clinical trials (AU)

Nanotechnology and the diagnosis/treatment of leishmaniasis / La nanotecnología y el diagnóstico/tratamiento de la leishmaniasis

Aim: The review article updates the current state of the art in the engineering of nanoplatforms against leishmaniasis. Special attention is devoted to the development of drug nanocarriers to be given to patients through the parenteral, topical, and oral routes of administration. Challenges and opportunities coming from advanced formulation methods/strategies introduced in the design of these nanosystems are emphasized. Finally, particular attention is also given to the use of nanoparticulate systems for vaccine delivery and for the diagnosis of the disease. Materials and Methods: To that aim, the Web sites of PubMed, HCAplus, Thomson, and Registry were used as the main sources to perform the search for the most significant research articles published on the subject. The information was then carefully analyzed, highlighting the most important preclinical results in the development of nanomedicines against leishmaniasis, as well considering vaccine delivery systems and nanoparticulate-based diagnosis. Results and Conclusion: The introduction of nanotechnology into the leishmaniasis arena is intended to optimize both the diagnosis and treatment (drug/vaccine therapy) of the disease. The objective is always to improve the selectivity of the imaging molecules or drugs/vaccines toward the parasite, especially when it is located inside phagocytic cells and neutrophils, while keeping to a very minimum the toxic side effects. Of course, only the wise engineering of the nanoparticulate delivery system will assure the best diagnostic/therapeutic outcomes

Objetivos: Este trabajo pretende actualizar la situación actual en el diseño de nanoplataformas contra la leishmaniasis. En este sentido, especial atención merecen los nanotransportadores de fármacos diseñados para ser administrados al paciente a través de las vías de administración parenteral, tópica y oral. Asimismo, se discuten las posibilidades que ofrecen las técnicas o estrategias de formulación más avanzadas en el diseño de estas nanoplataformas biomédicas. Finalmente, también se dedica especial atención a la utilización de estos nanosistemas en la administración de vacunas y en el diagnóstico de la leishmaniasis. Material y Métodos: Con este fin, se utilizaron las páginas Web PubMed, HCAplus, Thomson y Registry como principales fuentes para la búsqueda de los trabajos de investigación más interesantes publicados sobre la materia. La información así obtenida fue cuidadosamente analizada, resaltando aquellos resultados preclínicos más relevantes en cuanto al desarrollo de nanomedicamentos contra la leishmaniasis, y considerando también los nanosistemas transportadores de vacunas y las nanoplataformas de utilidad en el diagnóstico de esta enfermedad. Resultados y conclusiones: La nanotecnología es utilizada para mejorar el diagnóstico y tratamiento de la leishmaniasis. El objetivo es, en todos los casos, la mejora de la selectividad por el parásito de los fármacos, vacunas y moléculas utilizadas como agentes de contraste en técnicas de imagen, especialmente cuando este microorganismo se encuentra localizado en el interior de macrófagos y neutrófilos. Con esta interesante nanoherramienta, se puede también obtener una significativa reducción en la aparición y severidad de la toxicidad asociada a las técnicas de diagnóstico y tratamiento de la leishmaniasis. Es evidente que sólo con un inteligente diseño de estos nanosistemas se logran los mejores resultados de diagnóstico y terapia de la enfermedad

Skin permeation of cacalol, cacalone and 6-epi-cacalone sesquiterpenes from a nanoemulsion.

The objective of the present study was to investigate the transdermal permeation of cacalol (1) and a mixture of cacalone (2) and 6-epi-cacalone (3) in comparison with diclofenac acid (4) delivered from the same characterized nanoemulsion using Franz diffusion cells (formulae I, II and III). Results show that de Kp, J, Q24, PI and P2 were higher for the acid diclofenac nanoemulsion than for the natural products nanoemulsions. As for the differences between the formulations I and II, with the natural products, Q24, the quantity extracted from skin and P2 were higher in the mixture of 2 and 3 nanoemulsion compared with the corresponding nanoemulsion of 1. In conclusion, the low permeability of the natural products nanoemulsions in comparison with that of diclofenac acid has the potential for development for drugs with local and systemic applications, respectively.