TRAAC framework to improve regulatory acceptance and wider usability of tools and methods for safe innovation and sustainability of manufactured nanomaterials.

There has been an increasing use of advanced materials, particularly manufactured nanomaterials, in industrial applications and consumer products in the last two decades. It has instigated concerns about the sustainability, in particular, risks and uncertainties regarding the interactions of the manufactured nanomaterials with humans and the environment. Consequently, significant resources in Europe and beyond have been invested into the development of tools and methods to support risk mitigation and risk management, and thus facilitate the research and innovation process of manufactured nanomaterials. The level of risk analysis is increasing, including assessment of socio-economic impacts, and sustainability aspects, moving from a conventional risk-based approach to a wider safety-and-sustainability-by-design perspective. Despite these efforts on tools and methods development, the level of awareness and use of most of such tools and methods by stakeholders is still limited. Issues of regulatory compliance and acceptance, reliability and trust, user-friendliness and compatibility with the users' needs are some of the factors which have been traditionally known to hinder their widespread use. Therefore, a framework is presented to quantify the readiness of different tools and methods towards their wider regulatory acceptance and downstream use by different stakeholders. The framework diagnoses barriers which hinder regulatory acceptance and wider usability of a tool/method based on their Transparency, Reliability, Accessibility, Applicability and Completeness (TRAAC framework). Each TRAAC pillar consists of criteria which help in evaluating the overall quality of the tools and methods for their (i) compatibility with regulatory frameworks and (ii) usefulness and usability for end-users, through a calculated TRAAC score based on the assessment. Fourteen tools and methods were assessed using the TRAAC framework as proof-of-concept and for user variability testing. The results provide insights into any gaps, opportunities, and challenges in the context of each of the 5 pillars of the TRAAC framework. The framework could be, in principle, adapted and extended to the evaluation of other type of tools & methods, even beyond the case of nanomaterials.

[Neurological disorders and the blood-brain barrier. Strategies and limitations for drug delivery to the brain]. / Afecciones neurologicas y barrera hematoencefalica. Limitaciones y estrategias para la liberacion de farmacos al cerebro.

INTRODUCTION: The incidence in the central nervous system diseases has increased with a growing elderly population. Unfortunately, conventional treatments used to treat the mentioned diseases are frequently ineffective due to the presence of the blood brain barrier. AIM: To illustrate the blood-brain barrier properties that limit drug transport into the brain and the main strategies employed to treat neurologic disorders. DEVELOPMENT: The blood-brain barrier is mainly composed of a specialized microvascular endothelium and of glial cells. It constitutes a valuable tool to separate the central nervous system from the rest of the body. Nevertheless, it also represents an obstacle to the delivery of therapeutic drugs to the brain. CONCLUSIONS: To be effective, drugs must reach their target in the brain. On one hand, therapeutic agents could be designed to be able to cross the blood brain barrier. On the other hand, drug delivery systems could be employed to facilitate the therapeutic agents' entry into the central nervous system. In vivo models of neurological diseases, in addition to in vitro models of the blood brain barrier, have been widely employed for the evaluation of drugs utilized to treat central nervous system diseases.

TITLE: Afecciones neurologicas y barrera hematoencefalica. Limitaciones y estrategias para la liberacion de farmacos al cerebro.Introduccion. La incidencia de enfermedades del sistema nervioso central (SNC) aumenta a causa del envejecimiento de la sociedad. Desgraciadamente, los tratamientos clasicos para tratarlas no resultan efectivos debido a la presencia de la barrera hematoencefalica. Objetivo. Abordar las propiedades de la barrera hematoencefalica que impiden el transporte de los farmacos al cerebro y las principales estrategias para tratar las afecciones neurologicas. Desarrollo. La barrera hematoencefalica esta compuesta principalmente por un endotelio vascular especializado y las celulas de la glia. Esta constituye una herramienta a disposicion del organismo para aislar al SNC del resto del cuerpo. Sin embargo, tambien supone un impedimento para que muchos farmacos alcancen su diana en el cerebro. Conclusiones. Para poder tratar las afecciones neurologicas, los farmacos deben ser capaces de alcanzar el cerebro. Los agentes terapeuticos pueden diseñarse para que sean capaces de atravesar esta barrera, o bien facilitar su entrada mediante el uso de sistemas de liberacion. Para evaluar la efectividad de los tratamientos dirigidos a enfermedades del SNC, se emplean los modelos animales de enfermedades neurologicas asi como modelos in vitro de barrera hematoencefalica.