Biodegradable, antioxidant-loaded nanoparticles: a first step toward attenuating oxidative injury in vitro

Summary form only given. The relentless progression and devastating ramifications of neurodegenerative diseases make symptomatic and protective treatment of these ailments particularly critical and daunting. Parkinson's Disease (PD) is characterized by severe motor impairments, significant oxidative injury and degeneration of the nigrostriatal dopaminergic neurons. Although symptomatic PD therapy is initially effective, antioxidant treatments are more promising because they may decelerate and even prevent dopaminergic neurodegeneration. Therefore, we are developing antioxidant-loaded, biodegradable nanoparticles-drug delivery platforms that are advantageous as an antioxidant therapy to slow neurodegeneration. Innovations in bionanotechnology and drug delivery-areas that integrate bio engineering, materials science and cell biology-promise to revolutionize the treatment of neurodegenerative diseases like PD. In particular, drug-loaded, biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles are promising drug delivery devices because they protect unstable and poorly soluble drugs from the biological milieu, facilitate sustained drug levels in the vicinity of the nanoparticle and can be internalized by cells. We have synthesized novel Coenzyme Q10 (CoQ10)-loaded biodegradable PLGA nanoparticles with ester- and carboxylic acid- end groups by nanoprecipitation and characterized their physical properties with dynamic light scattering (DLS) and atomic force microscopy (AFM). We have consistently modulated the diameters of the nanoparticles between 100 nm and 200 nm by varying the PLGA mass in the solvent and the solvent/non-solvent volumetric ratio. These nanoparticle formulations were customarily monodisperse, with polydispersity indices <0.1. The CoQ10 incorporation efficiency was calculated spectrophotometrically by UV absorbance at 275 nm, and our preliminary data indicate successful encapsulation of CoQ10 within the nanoparticles. These results motivate further investigation of the CoQ10-loaded nanoparticles as drug delivery devices in a simple yet appropriate PD cell model. Thus, we are concurrently developing an oxidative injury model with dopaminergic PC12 cells in order to test the antioxidant effects of these CoQ10-loaded PLGA nanoparticles. Our CoQ10-loaded biodegradable PLGA nanoparticles may significantly enhance the prospects for neuronal drug therapy by attenuating dopaminergic oxidative damage and slowing the neurodegeneration associated with PD