title: Transdermal iontophoresis of flufenamic acid loaded PLGA nanoparticles.
abstract: The objective of this study was to test in vitro a drug delivery system that combines nanoencapsulation and iontophoresis for the transdermal delivery of lipophilic model drug using poly(lactic-co-glycolic acid) (PLGA) as the carrier polymer. Negatively charged fluorescent nanoparticles loaded with negatively charged flufenamic acid were prepared. The colloidal properties of the particles were stable under iontophoretic current (constant, pulsed and alternating) profiles and in contact with skin barrier. The release of the drug from the particles was not affected by iontophoresis and remained always limited (≈50%), leading to significantly lower transdermal fluxes across human epidermis and full thickness porcine skin compared to respective free drug formulation. From nanoparticles, pulsed current profile resulted in comparable or higher fluxes compared to constant current profile although fluorescence imaging was not able to confirm deeper distribution of nanoparticles in skin. Based on our results, there is no clear advantage with respect to drug permeation from nanoencapsulating flufenamic acid into PLGA nanoparticles compared to free drug formulation, either in passive or iontophoretic delivery regimens. However, pulsed current iontophoresis could be an effective alternative instead of traditional constant current iontophoresis to enhance transdermal permeation of drugs from nanoencapsulated formulations.
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland. Electronic address: kristina.malinovskaja@helsinki.fi.
authors.forename: K
authors.initials: K
authors.lastname: Malinovskaja-Gomez
authors.affiliation: Department of Chemistry, Faculty of Science and Cellular and Molecular Bioengineering Research Lab (CMBRL), Schulich School of Engineering, University of Calgary, 2500 University Dr NW, AB T2N 1N4 Calgary, Canada. Electronic address: h.labouta@ucalgary.ca.
authors.forename: H I
authors.initials: HI
authors.lastname: Labouta
authors.affiliation: Saarland University, Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Campus A4 1, D-66123 Saarbrücken, Germany. Electronic address: marc.schneider@mx.uni-saarland.de.
authors.forename: M
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland. Electronic address: jouni.hirvonen@helsinki.fi.
authors.forename: J
authors.initials: J
authors.lastname: Hirvonen
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland. Electronic address: timo.laaksonen@helsinki.fi.
authors.forename: T
authors.initials: T
authors.lastname: Laaksonen
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D005439:Flufenamic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D007478:Iontophoresis / Q000379:methods*; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption / Q000502:physiology; D013552:Swine
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005439:Flufenamic Acid
keywords: Iontophoresis; NSAID delivery; Nanotechnology; Poly(lactic-co-glycolic acid) nanoparticles; Skin permeation; Transdermal drug delivery