Nanoparticles and blood-brain barrier: the key to central nervous system diseases.

Major central nervous system disorders represent a significant and worldwide public health problem. In fact, the therapeutic success of many pharmaceuticals developed to treat central nervous system diseases is still moderate, since the blood-brain barrier (BBB) limits the access of systemically administered compounds to the brain. Therefore, they require the application of a large total dose of a drug, and cause numerous toxic effects. The development of nanotechnological systems are useful tools to deliver therapeutics and/or diagnostic probes to the brain due to nanocarriers having the potential to improve the therapeutic effect of drugs and to reduce their side effects. This review provides a brief overview of the variety of carriers employed for central nervous system drug and diagnostic probes delivery. Further, this paper focuses on the novel nanocarriers developed to enhance brain delivery across the blood-brain barrier. Special attention is paid to liposomes, micelles, polymeric and lipid-based nanoparticles, dendrimers and carbon nanotubes. The recent developments in nanocarrier implementation through size/charge optimization and surface modifications (PEGylation, targeting delivery, and coating with surfactants) have been discussed. And a detailed description of the nanoscaled pharmaceutical delivery devices employed for the treatment of central nervous system disorders have also been defined. The aim of the review is to evaluate the nanotechnology-based drug delivery strategies to treat different central nervous system disorders.

Afecciones neurológicas y barrera hematoencefálica. Limitaciones y estrategias para la liberación de fármacos al cerebro / Neurological disorders and the blood-brain barrier. Strategies and limitations for drug delivery to the brain

Introducción. La incidencia de enfermedades del sistema nervioso central (SNC) aumenta a causa del envejecimiento de la sociedad. Desgraciadamente, los tratamientos clásicos 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 fármacos al cerebro y las principales estrategias para tratar las afecciones neurológicas. Desarrollo. La barrera hematoencefalica está compuesta principalmente por un endotelio vascular especializado y las células de la glia. Esta constituye una herramienta a disposición del organismo para aislar al SNC del resto del cuerpo. Sin embargo, también supone un impedimento para que muchos fármacos alcancen su diana en el cerebro. Conclusiones. Para poder tratar las afecciones neurológicas, los fármacos deben ser capaces de alcanzar el cerebro. Los agentes terapéuticos pueden diseñarse para que sean capaces de atravesar esta barrera, o bien facilitar su entra mediante el uso de sistemas de liberación. Para evaluar la efectividad de los tratamientos dirigidos a enfermedades del SNC, se emplean los modelos animales de enfermedades neurológicas así como modelos in vitro de barrera hematoencefalica (AU)

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 (AU)

[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.