title: In vivo organ specific drug delivery with implantable peristaltic pumps.
abstract: Classic methods for delivery of agents to specific organs are technically challenging and causes superfluous stress. The current study describes a method using programmable, implantable peristaltic pumps to chronically deliver drugs in vivo, while allowing animals to remain undisturbed for accurate physiological measurements. In this study, two protocols were used to demonstrate accurate drug delivery to the renal medulla. First, the vasopressin receptor-2 agonist, dDAVP, was delivered to the renal medulla resulting in a significant increase in water retention, urine osmolality and aquaporin-2 expression and phosphorylation. Second, in a separate group of rats, the histone deacetylase (HDAC) inhibitor, MS275, was delivered to the renal medulla. HDAC inhibition resulted in a significant increase in histone H3-acetylation, the hallmark for histone deacetylase inhibition. However, this was confined to the medulla, as the histone H3-acetylation was similar in the cortex of vehicle and MS275 infused rats, suggesting targeted drug delivery without systemic spillover. Thus, implantable, peristaltic pumps provide a number of benefits compared to externalized chronic catheters and confer specific delivery to target organs.
authors.affiliation: Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Speed
authors.affiliation: Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Hyndman
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D050034:Antidiuretic Agents / Q000008:administration & dosage; D051399:Aquaporin 2 / Q000378:metabolism; D001549:Benzamides / Q000008:administration & dosage; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage; D006657:Histones / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D007679:Kidney Medulla / Q000187:drug effects / Q000502:physiology; D008297:Male; D009928:Organ Specificity; D009994:Osmolar Concentration; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D050034:Antidiuretic Agents; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D011725:Pyridines; C118739:entinostat; D003894:Deamino Arginine Vasopressin