title: Trans-scleral iontophoretic delivery of low molecular weight therapeutics.
abstract: The fundamental understanding of ocular drug delivery using iontophoresis is not at the same level as that for transdermal electrotransport. Research has therefore been undertaken to characterise the electrical properties of the sclera (charge, permselectivity, and isoelectric point (pI)) and to determine the basics of iontophoretic transport of model neutral, cationic, and anionic species (respectively, mannitol, timolol, and dexamethasone phosphate). Like the skin, the sclera supports a net negative charge under physiological pH conditions and has a pI between 3.5 and 4. Equally, the principles of trans-scleral iontophoretic transport of low molecular weight compounds are consistent with those observed for skin. Iontophoretic delivery of timolol and dexamethasone phosphate was proportional to applied current and drug concentration, and trans-scleral iontophoresis in rabbits led to enhanced intraocular levels of these compounds compared to passive delivery. The behaviour of higher molecular weight species such as peptide drugs and other biopharmaceuticals (e.g., proteins and oligonucleotides) has not been fully characterised. Further work has been undertaken, therefore, to examine the trans-scleral iontophoresis of vancomycin, a glycopeptide antibiotic with a relatively high molecular weight of 1448 Da. It was indeed possible to deliver vancomycin by iontophoresis but trans-scleral transport did not increase linearly with either increasing current density or peptide concentration.
authors.affiliation: Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: Sevgi
authors.initials: S
authors.lastname: Güngör
authors.forename: M Begoña
authors.initials: MB
authors.lastname: Delgado-Charro
authors.forename: Begoña
authors.initials: B
authors.lastname: Ruiz-Perez
authors.forename: William
authors.initials: W
authors.lastname: Schubert
authors.forename: Phil
authors.initials: P
authors.lastname: Isom
authors.forename: Peyman
authors.initials: P
authors.lastname: Moslemy
authors.forename: Michael A
authors.initials: MA
authors.lastname: Patane
authors.forename: Richard H
authors.initials: RH
authors.lastname: Guy
mesh_terms: D000818:Animals; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D004566:Electrodes; D004867:Equipment Design; D005260:Female; D066298:In Vitro Techniques; D007478:Iontophoresis; D008353:Mannitol / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits; D012590:Sclera / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D013999:Timolol / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D014640:Vancomycin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004364:Pharmaceutical Preparations; C004180:dexamethasone 21-phosphate; D008353:Mannitol; D014640:Vancomycin; D003907:Dexamethasone; D013999:Timolol