Articles

  • the Korean Society for Brain and Neural Sciences

Article

Original

Exp Neurobiol 2014; 23(3): 246-252

Published online September 30, 2014

https://doi.org/10.5607/en.2014.23.3.246

© The Korean Society for Brain and Neural Sciences

Increasing the Effciency of Parkinson’s Disease Treatment Using a poly(lactic-co-glycolic acid) (PLGA) Based L-DOPA Delivery System

P.Y. Gambaryan1*, I.G. Kondrasheva2, E.S. Severin2, A.A. Guseva1 and A.A. Kamensky1

1Biological Faculty, Moscow State University, 2Research Center for Molecular Diagnostics and Therapy, Moscow, Russia

Correspondence to: *To whom correspondence should be addressed.
TEL: 79032959480, FAX: 79032959480
e-mail: Serra_Avatar@list.ru

Received: July 2, 2014; Revised: August 20, 2014; Accepted: August 25, 2014

Abstract

To compare the efficacy of L-DOPA administered intranasally in the form of nanoparticles (nano-DOPA) and in standard drug forms using a rat Parkinson's Disease (PD) model. L-DOPA-containing nanoparticles (250±50 nm) were synthesized using the double emulsion method. The efficacy of nano-DOPA therapy was studied in Wistar rats with 6-OHDA-induced PD. Drugs were administered daily, 0.35 mg/kg (by L-DOPA). Animals' motor coordination and behavior were analyzed using the forelimb placing task and several other tests. Thirty minutes after the first administration, animals treated with L-DOPA, L-DOPA+benserazide, and nano-DOPA showed equally significant (p<0.05) improvements in coordination performance in comparison to the non-treated group. After 4 weeks of treatment, coordination performance in the nano-DOPA group (89±13% of the intact control level) was twice as high as in the L-DOPA and L-DOPA+benserazide groups, which did not differ from non-treated animals. The effect of nano-DOPA was significantly higher and more long-lasting (90±13% at 24 h after administration); moreover, it was still significant one week after the treatment was discontinued. Intranasal nano-DOPA was found to provide a lasting motor function recovery in the 6-OHDA-induced rat PD model with the effect sustained for one week after discontinuation, while the same doses of standard drugs provided significant effect only after the first administration. L-DOPA administered in the form of PLGA-based nanoparticles had a higher effective half-life, bioavailability, and efficacy; it was also efficiently delivered to the brain by intranasal administration.

Keywords: animal models, L-DOPA, Parkinson’s disease, nano-DOPA, PLGA, nasal administration