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La encapsulación y la unión covalente de la carga útil molecular en los nanoportadores micelares activados

Ido Rosenbaum¹, Assaf J Harnoy, Einat Tirosh

¹Department of Organic Chemistry, School of Chemistry, Faculty of Exact Sciences, ‡Department of Physical Chemistry, School of Chemistry, Faculty of Exact Sciences, §Tel Aviv University Center for Nanoscience and Nanotechnology, and ∥School of Physics and Astronomy, Faculty of Exact Sciences, Tel-Aviv University , Tel-Aviv 69978, Israel.

Journal of the American Chemical Society

|January 22, 2015

Resumen

Las micelas sensibles a las enzimas ofrecen una administración de fármacos ajustable. La encapsulación covalente proporciona una mayor capacidad y una liberación más lenta que los métodos no covalentes, mostrando el potencial para terapias dirigidas.

Área de la Ciencia:

Ciencia de los Biomateriales Ciencia de los Biomateriales.
Nanotecnología La nanotecnología es la nanotecnología.
Sistemas de suministro de drogas Sistemas de suministro de drogas.

Sus antecedentes:

Las enzimas sobreexpresadas en enfermedades son objetivos ideales para la liberación de fármacos que responden a estímulos.
Las drogas hidrofóbicas requieren sistemas nanocarrier efectivos para su administración.
Las micelas poliméricas ofrecen una plataforma versátil para encapsular y liberar agentes terapéuticos.

Objetivo del estudio:

Desarrollar y comparar dos distintas estrategias de nanocarrier micelares sensibles a las enzimas para la administración de fármacos hidrofóbicos.
Para investigar el impacto de la carga de fármaco no covalente versus covalente en el rendimiento de la micela.
Evaluar la capacidad de respuesta y la cinética de liberación de carga de los nanocarriers desarrollados.

Principales métodos:

Síntesis de híbridos poliméricos anfifílicos con polietilenglicol (PEG) y dendrones sensibles a la esterasa.
Preparación de micelas mediante autoensamblaje con carga hidrofóbica encapsulada no covalentemente o covalentemente unida (colorantes de cumarina).
Evaluación de la respuesta de las micelas al estímulo enzimático y cuantificación de las tasas de liberación de la carga.

Principales resultados:

Tanto las estrategias de carga no covalente como las covalentes dieron como resultado micelas sensibles a las enzimas que liberaron la carga tras el desencadenamiento enzimático.
La encapsulación no covalente condujo a una cinética de liberación de carga más rápida.
La encapsulación covalente demostró una mayor capacidad de carga de fármaco y una tasa de liberación más lenta y sostenida.

Conclusiones:

Las plataformas micelares sensibles a las enzimas son muy prometedoras para aplicaciones de administración de fármacos.
La elección de la estrategia de carga (no covalente vs. covalente) tiene un impacto significativo en la capacidad de carga útil y la cinética de liberación.
Estos sistemas ofrecen perfiles de liberación de fármacos ajustables, adaptables a necesidades terapéuticas específicas.

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