Trehalose Conjugated, Catechin Loaded Polylactide Nanoparticle for Improved Neuroprotection against Intracellular Polyglutamine Aggregate

nano technology — Lipid Nanoarchitectonics for Natural Products Delivery in Cancer Therapy

Intracellular/extracellular protein aggregation is linked to variety of neurodegenerative diseases. Current research focusses on identifying anti-amyloidogenic small molecules to inhibit such protein aggregation and associated cytotoxicity. We have recently demonstrated that transforming those anti-amyloidogenic small molecules into nanoparticle form can greatly improve their performance and biocompatible/biodegradable formulation of such nanoparticle is critical for therapeutic application.

Here we report, polylactide-based biodegradable nanoparticle for improved neuroprotection against polyglutamine aggregation that is responsible for Huntington’s disease. Polylactide is terminated with anti-amyloidogenic trehalose molecule or neurotransmitter dopamine and resultant nanoparticle is loaded with anti-amyloidogenic catechin molecule.

The self-assembled nanoparticle is ~200 nm in size that enters into neuronal cell, inhibits polyglutamine aggregation, lowers oxidative stress and enhances cell proliferation against polyglutamine aggregates. This biodegradable polymer can be used for making nanoformulation of other reported anti-amyloidogenic molecules for testing various animal models of neurodegenerative diseases.