Pharmaceutical Research

, Volume 29, Issue 9, pp 2367–2376 | Cite as

Preparation of Rotigotine-Loaded Microspheres and Their Combination Use with L-DOPA to Modify Dyskinesias in 6-OHDA-Lesioned Rats

  • Aiping Wang
  • Lexi Wang
  • Kaoxiang Sun
  • Wanhui Liu
  • Chunjie Sha
  • Youxin Li
Research Paper

ABSTRACT

Purpose

To prepare rotigotine loaded microspheres (RoMS) to achieve continuous dopaminergic stimulation (CDS) for the treatment of Parkinson’s disease (PD) and investigate both the therapeutic benefit and inducibility of AIMs of administration of RoMS combination with L-DOPA in 6-OHDA-leisioned rats.

Methods

Rotigotine was encapsulated into poly(lactic-co-glycolic acid) (PLGA) microspheres by an oil-in-water emulsion solvent evaporation technique. In vitro characteristics and in vivo pharmacokinetics of RoMS either in rat blood or brain (by microdialysis) were investigated. Contraversive rotations and AIMs were observed to investigate the therapeutic benefit and the propensity to induce dyskinesia of RoMS or RoMS combination with L-DOPA in 6-OHDA-lesioned rats.

Results

RoMS displayed continuous-release characteristics of rotigotine in animals and exhibited a steady efficacy lasted for 2 weeks in 6-OHDA-lesioned rats. No significant difference of the therapeutic benefit between the treatment of RoMS and pulsatile L-DOPA combination and mono L-DOPA was found. While the dyskinesia was significantly decreased with the treatment of RoMS and pulsatile L-DOPA combination compared to mono L-DOPA.

Conclusions

RoMS could supply an alternative of CDS for the treatment of PD and the study indicates a potential advantage of RoMS for the treatment of mild and advanced PD patient in combination with L-DOPA.

KEY WORDS

combination with L-DOPA continuous dopaminergic stimulation dyskinesia Parkinson’s disease rotigotine loaded microspheres 

ABBREVIATIONS

AIMs

abnormal involuntary movements

Apo

apomorphine

CDS

continuous dopaminergic stimulation

EE

encapsulation efficiency

im

intramuscular injection

ip

intraperitoneal injection

L-DOPA

levodopa

LID

levodopa induced dyskinesias

PD

Parkinson’s disease

PLGA

poly(lactic-co-glycolic acid)

po

per os

RoMS

rotigotine loaded microspheres

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Aiping Wang
    • 1
    • 2
  • Lexi Wang
    • 1
  • Kaoxiang Sun
    • 2
    • 3
  • Wanhui Liu
    • 2
    • 3
  • Chunjie Sha
    • 3
  • Youxin Li
    • 1
    • 3
  1. 1.College of Life ScienceJilin UniversityChangchunChina
  2. 2.School of PharmacyYantai UniversityYantaiChina
  3. 3.State Key Laboratory of Long-acting & Targeting Drug Delivery SystemYantaiChina

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