170 research outputs found

    Nanoparticles as carrier for improve therapeutic efficacy of pioglitazone in ocular inflammatory disorders: development and validation of a high throughput LC-MS/MS method for quantitation in ocular tissues

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    Abstract: Pioglitazone is an oral anti-hyperglycemic agent and it is used for the treatment of diabetes mellitus type 2. The anti-inflammatory activity has also been demonstrated in the literature. Pioglitazone belongs to Class II of Biopharmaceutical Classification System, i.e., slightly soluble and highly permeable. Polymeric nanoparticle formulations play an important role in the improvement of the efficacy of ocular therapies. These systems are non-toxic and biodegradable, show appropriate physicochemical characteristics as well as prolonged release profile suitable for ocular delivery. An accurate, sensitive, selective, reproducible and high throughput HPLC-MS/MS method was validated to quantitate pioglitazone in ocular tissues (cornea, sclera, lens, aqueous humour and vitreous humour). The chromatographic separation was achieved in 10 min on a Kinetex C18 column. Linear response of pioglitazone was observed over the range of 5-100 ng/ml. The limit of quantitation was 10 ng/ml (in extract). The recovery of pioglitazone or pioglitazone encapsulated in nanoparticles of polylactic-co-glycolic acid-polyethylene glycol (PLGA-PEG) was in the range 85-115 % in all tissues and levels tested. The intra-day and inter-day precision were <5 % and <10 % respectively. The obtained extracts demonstrated to be stable under various experimental conditions in all the studied matrices. This method can be applied to in vivo and ex vivo biodistribution studies related to the ocular administration of pioglitazone nanoparticles

    Microbial factories for recombinant pharmaceuticals

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    Most of the hosts used to produce the 151 recombinant pharmaceuticals so far approved for human use by the Food and Drug Administration (FDA) and/or by the European Medicines Agency (EMEA) are microbial cells, either bacteria or yeast. This fact indicates that despite the diverse bottlenecks and obstacles that microbial systems pose to the efficient production of functional mammalian proteins, namely lack or unconventional post-translational modifications, proteolytic instability, poor solubility and activation of cell stress responses, among others, they represent convenient and powerful tools for recombinant protein production. The entering into the market of a progressively increasing number of protein drugs produced in non-microbial systems has not impaired the development of products obtained in microbial cells, proving the robustness of the microbial set of cellular systems (so far Escherichia coli and Saccharomyces cerevisae) developed for protein drug production. We summarize here the nature, properties and applications of all those pharmaceuticals and the relevant features of the current and potential producing hosts, in a comparative wa

    On-line gas-diffusion separation and fluorimetric detection for the determination of acid dissociable cyanide

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    A flow injection system with gas diffusion separation and spectrofluorimetric detection is described for the determination of acid dissociable cyanide in waters. Cyanide diffuses through a microporous PTFE membrane from an acidic donor stream into a sodium hydroxide acceptor stream. The cyanide transferred reacts with o-phthalaldehyde and glycine to form a highly fluorescent isoindole derivative

    Towards Protein-Based Viral Mimetics for Cancer Therapies

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    High resistance and recurrence rates, along with elevated drug clearance, compel the use of maximum tolerated drug doses in cancer therapy, resulting in high-grade toxicities and limited clinical applicability. Promoting active drug accumulation in tumor tissues would minimize such issues and improve therapeutic outcomes. A new class of therapeutic drugs suitable for the task has emerged based on the concept of virus-mimetic nanocarriers, or 'artificial viruses.' Among the spectrum of materials under exploration in nanocarrier research, proteins offer unparalleled structural and functional versatility for designing viruslike molecular vehicles. By exhibiting 'smart' functions and biomimetic traits, protein-based nanocarriers will be a step ahead of the conventional drug-protein conjugates already in the clinics in ensuring efficient delivery of passenger antitumor drugs

    Student perceptions of gender mainstreaming in initial teacher training: a descriptive study

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    Introducción: A pesar de los esfuerzos para mejorar la calidad de la educación, la incorporación de la perspectiva de género (PG) en la formación inicial docente sigue estando ausente de los planes de estudio e ideario de las facultades de educación. Esta falta de atención al principio de igualdad representa una auténtica barrera para el logro de los Objetivos de Desarrollo Sostenible (Naciones Unidas, 2015) y para el desarrollo de una educación sensible al género. El propósito de este estudio fue explorar el grado de implementación del enfoque de género en la formación inicial de docentes desde la perspectiva del alumnado. Método: Con este fin (1) se diseñó y validó la escala de Evaluación Sensible a la Formación en Igualdad de Género (ESFIG) y (2) se administró a 601 docentes en formación de grado y máster (72% mujeres y 28% varones), edad media 24.31 años, de una universidad pública española. Resultados: Los resultados indicaron que (1) la ESFIG es un instrumento válido y adecuado para medir el grado de incorporación de la PG en la formación docente y (2) que los participantes perciben (a) la sensibilidad del centro a la implementación de la política de género de neutral e indiferente y (b) la preparación en género muy importante y necesaria para su formación; sin embargo, muestran una baja y poco realista percepción de la conciencia de desigualdades asociadas al género en los procesos de enseñanza-aprendizaje. Se hallaron diferencias estadísticamente significativas en las respuestas de los participantes en función de la titulación y el género. Discusión: Los resultados sustentan la utilidad de la ESFIG para su uso como un indicador del grado de incorporación de la PG en la docencia universitaria, así como un instrumento apto para identificar áreas de necesidad, orientar y evaluar el impacto de posibles acciones e intervenciones.Introduction: Despite government commitments to promote equality, gender mainstreaming (GM) in initial teacher preparation is still absent from curricula and thinking of the faculties of education. This little attention to the principle of equality represents a real barrier to achieve the Sustainable Development Goals (United Nations, 2015) and to develop and promote a gender-sensitive education. The purpose of this study was to explore the degree of implementation of the gender approach in initial teacher training from the student teacher’s perspective. Method: The Sensitive Assessment of Gender Equality Training (SAGET) scale was designed and validated, and then administered to 601 undergraduate and graduate student teachers (72% women and 28% male), mean age 24.31 years, from a Spanish public university. Results: Data revealed that (1) the SAGET is a valid and adequate instrument to measure the implementation status of gender mainstreaming in initial teacher education, and (2) that participants perceive neutrality and institutional indifference when implementing the gender approach in teaching; however, although they consider gender preparation necessary and very important for their education, they show a low and unrealistic perception of awareness of gender inequalities associated to the process of teaching and learning. Statistically significant differences were found in participant responses depending on degree and gender. Discussion: The results support the utility of the SAGET for its use as an indicator of gender mainstreaming in university teaching as well as a suitable instrument to identify areas of need and assess the impact of future actions and interventions.Este estudio fue financiado por el Vicerrectorado de Calidad e Innovación Educativa (Instituto de Ciencias de la Educación) de la Universidad de Alicante, en el marco del programa Redes I3CE de investigación en docencia universitaria (Ref. 2018-2019/4413) y por el Instituto Universitario de Investigación de Estudios de Género, programa de Ayudas para el Desarrollo de Actividades Conducentes a la Realización de Tesis Doctorales (BOUA, 21/11/2019)

    Biological activities of histidine-rich peptides; merging biotechnology and nanomedicine

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    Histidine-rich peptides are commonly used in recombinant protein production as purification tags, allowing the one-step affinity separation of the His-tagged proteins from the extracellular media or cell extracts. Genetic engineering makes feasible the post-purification His-tag removal by inserting, between the tag and the main protein body, a target site for trans-acting proteases or a self-proteolytic peptide with regulatable activities. However, for technical ease, His tags are often not removed and the fusion proteins eventually used in this form. In this commentary, we revise the powerful biological properties of histidine-rich peptides as endosomolytic agents and as architectonic tags in nanoparticle formation, for which they are exploited in drug delivery and other nanomedical applications. These activities, generally unknown to biotechnologists, can unwillingly modulate the functionality and biotechnological performance of recombinant proteins in which they remain trivially attached

    BBB-targeting, protein-based nanomedicines for drug and nucleic acid delivery to the CNS

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    The increasing incidence of diseases affecting the central nervous system (CNS) demands the urgent development of efficient drugs. While many of these medicines are already available, the Blood Brain Barrier and to a lesser extent, the Blood Spinal Cord Barrier pose physical and biological limitations to their diffusion to reach target tissues. Therefore, efforts are needed not only to address drug development but specially to design suitable vehicles for delivery into the CNS through systemic administration. In the context of the functional and structural versatility of proteins, recent advances in their biological fabrication and a better comprehension of the physiology of the CNS offer a plethora of opportunities for the construction and tailoring of plain nanoconjugates and of more complex nanosized vehicles able to cross these barriers. We revise here how the engineering of functional proteins offers drug delivery tools for specific CNS diseases and more transversally, how proteins can be engineered into smart nanoparticles or 'artificial viruses' to afford therapeutic requirements through alternative administration routes
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