title: Drug adsorption on bovine and porcine sclera studied with streaming potential.
abstract: The affinity of a drug to a biological membrane can affect the distribution and the availability of the active compound to its target. Adsorption is usually determined with in vitro distribution studies based on partitioning of the drug between buffer and tissue, which have limitations such as the high variability of the uptake data and the need for high accuracy in the measurement of drug concentration. Furthermore, distribution studies yield solute concentrations in the bulk of the tissue, whereas electrokinetic phenomena such as streaming potential and electroosmosis reflect the electric charge density on a membrane surface. Streaming potential thus can be used in studying the conditions, by which the charge sign and density can be regulated. That, in turn, has significance to electroosmotic transport mechanism during iontophoresis. In this communication, the adsorption of model compounds methylprednisolone sodium succinate, propranolol, and cytochrome C on bovine and porcine sclera is determined as a function of their concentration by measuring streaming potential. Both membranes had negative streaming potential, proving that they carry negative charge, but had different values at negative and positive pressure differences, which is addressed to the structural asymmetry of these membranes. Bovine sclera had a clearly higher value of streaming potential, ca. -26 nV/Pa, than porcine sclera, ca. -7 nV/Pa (10 mM NaCl solution). All the model compounds were adsorbed on bovine and porcine sclera already in the millimolar concentration range and can have an impact to electroosmosis during transscleral iontophoresis. The results obtained help to better elucidate the phenomena involved in transscleral transport, both in passive diffusion and in iontophoresis, supporting the future application of iontophoresis to the noninvasive delivery of drugs to the posterior segment of the human eye.
authors.affiliation: Aalto University, Department of Chemistry, Aalto FI-00076, Finland. lasse.murtomaki@aalto.fi
authors.forename: Lasse
authors.initials: L
authors.lastname: Murtomäki
authors.forename: Tuomas
authors.initials: T
authors.lastname: Vainikka
authors.forename: Silvia
authors.initials: S
authors.lastname: Pescina
authors.forename: Sara
authors.initials: S
authors.lastname: Nicoli
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000327:Adsorption; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002417:Cattle; D045304:Cytochromes c / Q000008:administration & dosage* / Q000493:pharmacokinetics; D053841:Electroosmosis; D004867:Equipment Design; D006801:Humans; D007478:Iontophoresis; D008776:Methylprednisolone Hemisuccinate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010539:Permeability; D011433:Propranolol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012590:Sclera / Q000378:metabolism*; D013552:Swine
chemical_list: D000319:Adrenergic beta-Antagonists; D000893:Anti-Inflammatory Agents; D008776:Methylprednisolone Hemisuccinate; D045304:Cytochromes c; D011433:Propranolol