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Continuous Transdermal Delivery of L-DOPA Based on a Self-Assembling Nanomicellar System

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Abstract

Purpose

When levodopa (L-DOPA) is administered orally, it is eliminated from the body very quickly resulting in a series of sharp fluctuations in its blood concentrations. These frequent changes in blood levels are considered to be responsible for the development of late motor complications and dyskinesias, which are troubling clinical and treatment issues in Parkinson’s disease. Transdermal drug delivery is a patient-compliant method for delivering therapeutics into the systemic circulation in a continuous and controlled manner. Transdermal delivery of L-DOPA can achieve continuous dopaminergic stimulation (CDS), thus reducing motor fluctuations.

Methods

However, there are two technical difficulties in the development of a transdermal patch for L-DOPA: (a) L-DOPA is poorly soluble in most pharmaceutically-acceptable solvents, and (b) L-DOPA has a limited permeability through the skin even from saturated solutions. We have, therefore, investigated the transdermal delivery of L-DOPA using an innovative self-assembling nano-micellar system (SANS), loaded with 2% L-DOPA and 1% carbidopa.

Results

In vitro testing as well as in vivo pharmacokinetic studies (multiple-dose regimen) in rabbits have demonstrated for the first time a significantly increased percutaneous permeation and systemic absorption of L-DOPA.

Conclusions

It has therefore been proposed that either a once-daily or a twice-daily regimen could be therapeutically effective depending on the severity of the disease.

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Abbreviations

CDS:

Continuous dopaminergic stimulation

CoS/S:

Co-surfactant/surfactants ratio

DLS:

Dynamic light scattering

HPLC:

High-performance liquid chromatography

L-DOPA:

L-3,4-dihydroxyphenylalanine, levodopa

LID:

Levodopa-induced diskynesia

PBS:

Phosphate buffer saline

PD:

Parkinson’s disease

SANS:

Self-assembling nanomicellar system

TEM:

Transmission electron microscopy

TEWL:

Transepidermal water loss

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Acknowledgements and Disclosures

This work was granted the Dekker Foundation Award in Parkinson’s Disease Research through The Bachmann-Strauss Dystonia & Parkinson Foundation, Inc., New York, NY. The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Faculty of Engineering Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Be’er Sheva, 84105, Israel

    Amnon C. Sintov

  2. Laboratory for Biopharmaceutics, Ben Gurion University of the Negev, E.D. Bergmann Campus, P.O. Box 653, Be’er Sheva, 84105, Israel

    Amnon C. Sintov & Igor Greenberg

  3. NanoDerma Ltd., Raanana, Israel

    Haim V. Levy

Authors
  1. Amnon C. Sintov
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  2. Haim V. Levy
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  3. Igor Greenberg
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Correspondence to Amnon C. Sintov.

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Sintov, A.C., Levy, H.V. & Greenberg, I. Continuous Transdermal Delivery of L-DOPA Based on a Self-Assembling Nanomicellar System. Pharm Res 34, 1459–1468 (2017). https://doi.org/10.1007/s11095-017-2162-y

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  • DOI: https://doi.org/10.1007/s11095-017-2162-y

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