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  • Title: Continuous Transdermal Delivery of L-DOPA Based on a Self-Assembling Nanomicellar System.
    Author: Sintov AC, Levy HV, Greenberg I.
    Journal: Pharm Res; 2017 Jul; 34(7):1459-1468. PubMed ID: 28405912.
    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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