Personalized nanomedicine: a revolution at the nanoscale

Nanomedicine is an interdisciplinary research field that results from the application of nanotechnology to medicine and has the potential to significantly improve some current treatments. Specifically, in the field of personalized medicine, it is expected to have a great impact in the near future due to its multiple advantages, namely its versatility to adapt a drug to a cohort of patients. In the present review, the properties and requirements of pharmaceutical dosage forms at the nanoscale, so-called nanomedicines, are been highlighted. An overview of the main current nanomedicines in pre-clinical and clinical development is presented, detailing the challenges to the personalization of these therapies. Next, the process of development of novel nanomedicines is described, from their design in research labs to their arrival on the market, including considerations for the design of nanomedicines adapted to the requirements of the market to achieve safe, effective, and quality products. Finally, attention is given to the point of view of the pharmaceutical industry, including regulation issues applied to the specific case of personalized medicine. The authors expect this review to be a useful overview of the current state of the art of nanomedicine research and industrial production, and the future opportunities of personalized medicine in the upcoming years. The authors encourage the development and marketing of novel personalized nanomedicines

Complex pBAE Nanoparticle Cell Trafficking: Tracking Both Position and Composition Using Super Resolution Microscopy

Nanomedicine emerged some decades ago with the hope to be the solution for most unmet medical needs. However, tracking materials at nanoscale is challenging to their reduced size, below the resolution limit of most conventional techniques. In this context, we propose the use of direct stochastic optical reconstruction microscopy (dSTORM) to study time stability and cell trafficking after transfection of oligopeptide end-modified poly(?-aminoester) (OM-pBAE) nanoparticles. We selected different combinations of cationic end oligopeptides (arginine - R; histidine - H; and lysine - K) among polymer libraries, since the oligopeptide combination demonstrated to be useful for different applications, such as vaccination and gene silencing. We demonstrate that their time evolution as well as their cell uptake and trafficking are dependent on the oligopeptide. This study opens the pave to broad mechanistic studies at nanoscale that could enable a rational selection of specific pBAE nanoparticles composition after determining their stability and cell trafficking.© 2022 The Authors. ChemMedChem published by Wiley-VCH GmbH

Contribuição docente no desenho de Ambientes Virtuais Colaborativos para educação pré-escolar

El uso de la tecnología ha representado un cambio en varios ámbitos cotidianos; entre esos, la educación. Para la educación preescolar, se propone que el ingreso de herramientas como la computadora, sea a través del aprendizaje colaborativo. La presente investigación muestra los resultados del diseño de un prototipo de juego que promueve la colaboración entre niños de nivel preescolar. Por medio de grupos focales, 21 docentes de dos centros educativos especializados en preescolar de San José, Costa Rica, fueron criterio experto y aportaron en el diseño de escenarios, obstáculos, música y texturas del videojuego; además, participaron de talleres donde se desarrollaron tres ejes teóricos: colaboración, tecnología y desarrollo sociocognitivo.The use of technology has represented a change in several daily areas; like education. In preschool education case, technologic tools as computers insertion are proposed through the use of collaborative learning. Present research shows the result of the design of a collaborative game prototype, which supports collaboration among preschool children. Through focal groups, 21 teachers of two educative centers that specialize in preschool education in San José city in Costa Rica, participated as expert judgment and contributed in the scenario design, obstacles, music and textures of the game. These teachers also participated in workshops where three axes were developed: collaboration, technology and sociocognitive development.O uso da tecnologia representou uma mudança em várias áreas do cotidiano; dentre elas, na educação. Para a educação pré-escolar, propõe-se que a entrada de ferramentas como o computador, seja através da aprendizagem colaborativa. Esta pesquisa mostra os resultados do desenho de um protótipo de jogo que promove a colaboração entre crianças de nível pré-escolar. Através de grupos focais, 21 professores de dois centros educativos especializados em pré-escolar de San José, na Costa Rica, foram critério experto e contribuíram no desenho de cenários, obstáculos, música e texturas do videogame. Eles também participaram de oficinas onde foram desenvolvidos três eixos teóricos: colaboração, tecnologia e desenvolvimento sócio-cognitivo.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Neurociencias (CIN)UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Instituto de Investigaciones Sociales (IIS

Tecnología en preescolar: de las iniciativas autogestionadas al diseño de aplicaciones educativas

Hoy en día, en el mundo entero, y como una consecuencia de la inserción de las Tecnologías de la Información y la Comunicación (TIC) en la sociedad, hay una tendencia cada vez mayor por intentar introducir la tecnología en la educación. Costa Rica no es la excepción, y es por eso que han existido esfuerzos para la alfabetización tecnológica, que consiste en un acercamiento a los usuarios para mejorar el acceso y el uso de la tecnología; en este caso, la computadora. En preescolar también existen esfuerzos, aunque menos numerosos, para integrar la computadora dentro de la dinámica de aula. La presente ponencia resume dos iniciativas: la primera que rescata las experiencias de docentes para equipar sus aulas con computadoras y el uso de ésta como herramienta y la segunda que representa un con tres agentes relevantes para la inserción de la computadora en el aula, que son la alfabetización tecnológica, los ambientes virtuales colaborativos (como software educativo para preescolar) y el desarrollo sociocognitivo (componente esencial en la colaboración).UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Neurociencias (CIN

Development of multifunctional polymeric nanoparticles by nano-emulsion templating as advanced nanocarriers targeting the blood-brain barrier

[cat] Les nanopartícules polimèriques multifuncionals (NPs) representen una alternativa prometedora pel tractament de malalties neurodegeneratives, a través de l’administració intravenosa (i.v.), ja que els tractaments actuals provoquen molts efectes secundaris. Les NPs, en canvi, si estan correctament dissenyades, poden actuar específicament en el teixit diana. Ja que l’òrgan diana és el cervell, és necessari un element de vectorització per poder creuar la barrera hemato-encefàlica (BBB). En aquest context, l’objectiu de la present tesi és l’obtenció de NPs com a sistemes avançats d’alliberament de principis actius que travessin la BBB. Es van obtenir NPs a partir de nano-emulsions (NE) plantilla, emprant l’àcid poli-(làctic-co-glicòlic) com a polímer i el mètode d’inversió de fases a temperatura constant per emulsionar, seguit d’evaporació de solvent per obtenir NPs. Les NPs obtingudes tenen mides apropiades per l’administració i.v.. Es va aconseguir encapsular un fluorescent i NPs magnètiques dins les NPs polimèriques, per fer-les servir com a sistemes d’imatge. També es van encapsular fàrmacs per usar-les com a sistemes terapèutics. En tots els casos, es van aconseguir eficiències d’encapsulació molt elevades i un alliberament del fàrmac controlat i prolongat en el temps. A més, es va aconseguir funcionalitzar la superfície de les NPs amb diferents elements. Es van unir covalentment dendrons catiònics per posteriorment unir oligonucleòtids electrostàticament. També es va afegir una coberta exterior de polietilenglicol per protegir el material genètic. Per altra banda, es va funcionalitzar la superfície de les NPs amb un anticòs específic contra el receptor de la transferrina, sobreexpressat a la BBB. A continuació, es van fer assajos in vitro, que van posar de manifest que les NPs no són citotòxiques ni hemolítiques. També es va estudiar l’eficiència de transfecció cel•lular del material genètic, arribant a eficiències de transfecció equivalents a les dels vectors comercials. Assajos in vivo van permetre confirmar el pas a través de la BBB, sobretot de les NPs funcionalitzades amb l’anticòs. Els resultats obtinguts permeten concloure que s’ha aconseguit dissenyar noves NPs polimèriques a partir de NE, apropiades per l’administració i.v. i amb capacitat de travessar la BBB.[eng] Multifunctional polymeric nanoparticles (NP) represent a promising alternative for the treatment of neurodegenerative diseases using the intravenous route (i.v.). In current treatments, the effects of the intravenously injected drugs are systemic, requiring high drug doses to achieve therapeutic effects, thus causing severe side effects. NP can act specifically in a tissue provided that they are properly designed. An interesting approach is the preparation of NPs by nano-emulsion templating. Nano-emulsions (NE) are fine emulsions, with droplet sizes typically between 20 – 200nm. They can be prepared by the phase inversion composition (PIC) method, a low-energy emulsification method appropriate for pharmaceutical applications, since it can be performed at mild process conditions. Nanoparticles are obtained from nano-emulsions by solvent evaporation. To target the central nervous system (CNS), a specific targeting moiety on the nanoparticle surface is required to cross the blood-brain barrier (BBB), which is a current key goal under intense investigations. The aim of this work was to obtain multifunctional polymeric NP as advanced delivery systems able to cross the BBB. O/W polymeric NE were prepared by the PIC method and polymeric NPs were obtained by solvent evaporation. Polymeric NP with appropriate sizes for the i.v. administration (<1milimicron) were obtained. With the aim to design imaging systems, a model fluorescent dye and magnetic nanoparticles were encapsulated in polymeric NPs. An analgesic and an antiapoptotic drugs were also encapsulated into PLGA NP for therapeutic purposes. High encapsulation efficiencies were found for all tested compounds, attributed to the method of nanoparticle preparation as well as to low solubility of the components in the aqueous dispersion media. In addition, a sustained and controlled release of fluorescent dyes / drugs was achieved. NP surface was functionalized using various elements. On the one hand, it was functionalized with a monoclonal antibody against the transferring receptor, overexpressed in the BBB, to achieve an active targeting to the BBB. On the other hand, NPs were functionalized with oligonucleotides, to be used as non-viral gene delivery systems. Firstly, carbosilane cationic dendrons were covalently attached to nanoparticle surface to achieve a cationic surface. In a further step, antisense oligonucleotides, siRNA and plasmids were electrostatically bound to cationized nanoparticles. In vitro tests showed that the formulated NP did produce neither cytoxicity nor hemolysis. In addition, they were weak activators of the immune system and produced only a slight adsorption of blood proteins. Therefore, they are appropriate to be used by the i.v. route. NPs functionalized with oligonucleotides enhanced gene transfection in cell cultures, up to values comparable to those of commercial values (up to 90%). These NPs are advantageous in terms of toxicity issues over the commercial formulations. Therefore, they represent promising non-viral gene delivery systems. In vivo tests, which measured the central analgesia produced by an encapsulated drug into nanoparticles (loperamide) that is not able to cross the BBB, confirmed a central analgesic effect, reaching a potency of analgesia comparable to positive controls when nanoparticles were functionalized with the antibody. Therefore, the antibody functionalized nanoparticles efficiently crossed the BBB. In conclusion, the designed polymeric nanoparticles, functionalized with the antitransferrin receptor antibody, are able to cross the BBB with high efficiency. These nanoparticles represent promising nanosystems to deliver actives to the central nervous system

Methods for the In Vitro Characterization of Nanomedicines—Biological Component Interaction

The design of colloidal nanosystems intended for biomedical applications, specifically in the field of personalized medicine, has increased notably in the last years. Consequently, a variety of characterization techniques devoted to studying nanomedicine interactions with proteins and cells have been developed, since a deep characterization of nanosystems is required before starting preclinical and clinical studies. In this context, this review aims to summarize the main techniques used to assess the interaction of nanomedicines with biological systems, highlighting their advantages and disadvantages. Testing designed nanomaterials with these techniques is required in order to have more information about their behavior on a physiological environment. Moreover, techniques used to study the interaction of nanomedicines with proteins, such as albumin and fibrinogen, are summarized. These interactions are not desired, since they usually are the first signal to the body for the activation of the immune system, which leads to the clearance of the exogenous components. On the other hand, techniques for studying the cell toxicity of nanosystems are also summarized, since this information is required before starting preclinical steps. The translation of knowledge from novel designed nanosystems at a research laboratory scale to real human therapies is usually a limiting or even a final point due to the lack of systematic studies regarding these two aspects: nanoparticle interaction with biological components and nanoparticle cytotoxicity. In conclusion, this review will be a useful support for those scientists aiming to develop nanosystems for nanomedicine purposes.Financial support from the Spanish Ministry of Economy and Competitivity, MINECO (grant CTQ2014-52687-C-1-P and CTQ2016-80645-R) and Generaltitat de Catalunya (grant 2014-SGR-1655) is acknowledged. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, and CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)

Una investigación visual sobre el Proyecto Integrado de Aula y la incorporación de tecnologías digitales en la educación primaria

[spa] Esta tesis doctoral es el resultado de una investigación educativa realizada con la comunidad académica del Colegio Unidad Pedagógica (Bogotá, Colombia). A partir de un interés compartido, entre la investigadora y la comunidad, por explorar la integración de las tecnologías digitales en el aula de clase, se planteó un estudio de caso sobre una intervención participativa desarrollada a lo largo de un año académico. El trabajo con la comunidad se llevó a cabo en distintos niveles y ámbitos, según las necesidades e intereses tanto de los docentes como los estudiantes. En este informe, se analiza el proyecto desarrollado con un grupo de 19 estudiantes, entre los 11 y 12 años, y su maestra; se llevó a cabo siguiendo la metodología del Proyecto Integrado de Aula, que es la propuesta curricular que se trabaja en el Colegio desde los 3 hasta los 12 años. El análisis del caso se llevó a cabo desde el marco epistemológico y metodológico de la Teoría del Actor-Red. Los resultados se presentan en tres diálogos sobre tres dimensiones particulares de la intervención. El primero se enfoca en la comunidad académica como contexto de investigación: el diálogo se establece a través del análisis de eventos y prácticas por fuera del aula de clase, trazando los actores discursivos, materiales y humanos que las componen. El segundo se enfoca en el Proyecto Integrado de Aula desarrollado con los estudiantes y su maestra: el diálogo se establece entre las prácticas y eventos que sucedieron dentro del aula y los referentes teóricos sobre los cuales se formuló la propuesta pedagógica de la institución. Por último, se propone una reflexión que conecta los resultados del análisis de la metodología del Proyecto Integrado de Aula y algunos discursos clave en innovación pedagógica con uso de tecnologías digitales. Teniendo en cuenta que muchos discursos contemporáneos sobre educación se enfocan en el uso de tecnologías digitales como actores claves en la innovación pedagógica, esta investigación busca abrir caminos de reflexión sobre esta integración. La metodología del Proyecto Integrado de Aula, las maneras de hacer y de entender que la sostienen, se presentan como una propuesta alternativa a la corriente de integración de tecnologías digitales masificada en las aulas de clase