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

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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.

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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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ACKNOWLEDGMENTS & DISCLOSURES

This work was supported by the National Basic Research Program of China (973 Program No. 2012CB724003) and Yantai University (grants YX11Z1).

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Authors and Affiliations

  1. College of Life Science, Jilin University, NO.2699 Qianjin Street, 130012, Changchun, Jilin Province, China

    Aiping Wang, Lexi Wang & Youxin Li

  2. School of Pharmacy, Yantai University, No. 32 Qingquan Road, 264005, Yantai, Shandong Province, China

    Aiping Wang, Kaoxiang Sun & Wanhui Liu

  3. State Key Laboratory of Long-acting & Targeting Drug Delivery System, No. 9 Baoyuan Road, 264003, Yantai, Shandong Province, China

    Kaoxiang Sun, Wanhui Liu, Chunjie Sha & Youxin Li

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  1. Aiping Wang
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  2. Lexi Wang
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  4. Wanhui Liu
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Correspondence to Youxin Li.

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Aiping Wang and Lexi Wang contributed equally to this work.

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Wang, A., Wang, L., Sun, K. et al. Preparation of Rotigotine-Loaded Microspheres and Their Combination Use with L-DOPA to Modify Dyskinesias in 6-OHDA-Lesioned Rats. Pharm Res 29, 2367–2376 (2012). https://doi.org/10.1007/s11095-012-0762-0

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  • DOI: https://doi.org/10.1007/s11095-012-0762-0

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