title: Increasing the Efficiency of Parkinson's Disease Treatment Using a poly(lactic-co-glycolic acid) (PLGA) Based L-DOPA Delivery System.
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.
authors.affiliation: Biological Faculty, Moscow State University, Moscow, Russia.
authors.forename: P Y
authors.initials: PY
authors.lastname: Gambaryan
authors.affiliation: Research Center for Molecular Diagnostics and Therapy, Moscow, Russia.
authors.forename: I G
authors.initials: IG
authors.lastname: Kondrasheva
authors.affiliation: Research Center for Molecular Diagnostics and Therapy, Moscow, Russia.
authors.forename: E S
authors.initials: ES
authors.lastname: Severin
authors.affiliation: Biological Faculty, Moscow State University, Moscow, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Guseva
authors.affiliation: Biological Faculty, Moscow State University, Moscow, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Kamensky
keywords: L-DOPA; PLGA; Parkinson's disease; animal models; nano-DOPA; nasal administration