title: AC electrokinetic platform for iontophoretic transdermal drug delivery.
abstract: Iontophoretic and electroporation transdermal delivery modes of ionic drugs have been utilized in a number of clinical and biomedical devices. However, applications of these methods have been found challenging for the delivery of many non polar and high molecular weight clinically important drugs. The main goal of the present study is to investigate whether transdermal transport of non polar macromolecular drugs such as insulin and terbinafine can be safely enhanced as a result of their polarization and activation by AC electrokinetic forces. An in vitro delivery system was developed to simulate a clinical application, where transdermal non invasive delivery of medication through a biological membrane is motivated by a combination of AC electrokinetic and AC iontophoresis protocols generated on a device located external to the membrane. The developed method resulted in an average transdermal delivery of 57% of insulin and 39% of terbinafine during several minutes long delivery cycle, which is at least an order of magnitude improvement over the results reported for these drugs in the literature for various passive and active transdermal delivery protocols. For the proposed drug delivery model quantification of the amounts of transported drugs and their relationship to experimental parameters, such as AC voltage amplitude and frequency, treatment time, and membrane thickness were investigated. Experimental results validated a computational model simulating the effects of major electrokinetic forces on drug particle in non uniform AC electric field. The presented transdermal approach overcomes many limitations of existing drug delivery technologies, providing efficient, regulated, localized, non invasive and safe delivery method for high molecular weight non polar macromolecules such as insulin.
authors.affiliation: The Cleveland Clinic Foundation, Department of Biomedical Engineering, ND20, 9500 Euclid Ave., Cleveland, OH 44195, United States. lvovicv@ccf.org
authors.forename: Vadim F
authors.initials: VF
authors.lastname: Lvovich
authors.forename: Ellen
authors.initials: E
authors.lastname: Matthews
authors.forename: Alan T
authors.initials: AT
authors.lastname: Riga
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Kaza
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002417:Cattle; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D006724:Hoof and Claw / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage; D007478:Iontophoresis / Q000295:instrumentation / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D013552:Swine
chemical_list: D007328:Insulin; D004364:Pharmaceutical Preparations