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Drug Dev Ind Pharm. 2017 Jun;43(6):871-888. doi: 10.1080/03639045.2017.1281949. Epub 2017 Jan 31.

Nanoparticulate strategies for the treatment of polyglutamine diseases by halting the protein aggregation process.

Author information

1
a Laboratorio de Investigación y Posgrado en Tecnología Farmacéutica, Facultad de Estudios Superiores Cuautitlán , Universidad Nacional Autónoma de México (UNAM) , Cuautitlán Izcalli , Mexico.
2
b Laboratory of Connective Tissue , CENIAQ, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra , Mexico City , Mexico.
3
c Department of Genetics and Molecular Biology , CINVESTAV-IPN , Mexico City , Mexico.
4
d División de Estudios de Posgrado (Tecnología Farmacéutica), Facultad de Estudios Superiores Cuautitlán , Universidad Nacional Autónoma de México (UNAM) , Cuautitlán Izcalli , Mexico.
5
e Laboratory of Genomic Medicine, Department of Genetics , Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra , Mexico City , Mexico.

Abstract

Polyglutamine (polyQ) diseases are a class of neurodegenerative disorders that cause cellular dysfunction and, eventually, neuronal death in specific regions of the brain. Neurodegeneration is linked to the misfolding and aggregation of expanded polyQ-containing proteins, and their inhibition is one of major therapeutic strategies used commonly. However, successful treatment has been limited to date because of the intrinsic properties of therapeutic agents (poor water solubility, low bioavailability, poor pharmacokinetic properties), and difficulty in crossing physiological barriers, including the blood-brain barrier (BBB). In order to solve these problems, nanoparticulate systems with dimensions of 1-1000 nm able to incorporate small and macromolecules with therapeutic value, to protect and deliver them directly to the brain, have recently been developed, but their use for targeting polyQ disease-mediated protein misfolding and aggregation remains scarce. This review provides an update of the polyQ protein aggregation process and the development of therapeutic strategies for halting it. The main features that a nanoparticulate system should possess in order to enhance brain delivery are discussed, as well as the different types of materials utilized to produce them. The final part of this review focuses on the potential application of nanoparticulate system strategies to improve the specific and efficient delivery of therapeutic agents to the brain for the treatment of polyQ diseases.

KEYWORDS:

PolyQ diseases; blood–brain barrier; brain; nanoparticulate systems; nanotechnology; protein aggregation; therapeutic agents

PMID:
28142290
DOI:
10.1080/03639045.2017.1281949
[Indexed for MEDLINE]

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