title: Continuous Transdermal Delivery of L-DOPA Based on a Self-Assembling Nanomicellar System.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Be'er Sheva, 84105, Israel. asintov@bgu.ac.il.|Laboratory for Biopharmaceutics, Ben Gurion University of the Negev, E.D. Bergmann Campus, P.O. Box 653, Be'er Sheva, 84105, Israel. asintov@bgu.ac.il.
authors.forename: Amnon C
authors.initials: AC
authors.lastname: Sintov
authors.affiliation: NanoDerma Ltd., Raanana, Israel.
authors.forename: Haim V
authors.initials: HV
authors.lastname: Levy
authors.affiliation: Laboratory for Biopharmaceutics, Ben Gurion University of the Negev, E.D. Bergmann Campus, P.O. Box 653, Be'er Sheva, 84105, Israel.
authors.forename: Igor
authors.initials: I
authors.lastname: Greenberg
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000978:Antiparkinson Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002230:Carbidopa / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers; D004338:Drug Combinations; D065546:Drug Liberation; D007980:Levodopa / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008823:Micelles; D053758:Nanoparticles; D010539:Permeability; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption; D013499:Surface Properties; D013552:Swine; D057968:Transdermal Patch
chemical_list: D000978:Antiparkinson Agents; D004337:Drug Carriers; D004338:Drug Combinations; D008823:Micelles; D007980:Levodopa; D002230:Carbidopa
keywords: Carbidopa; Parkinson’s disease; levodopa; transdermal drug delivery