title: Nonaqueous gel for the transdermal delivery of a DTPA penta-ethyl ester prodrug.
abstract: Diethylenetriamine pentaacetic acid penta-ethyl ester, designated as C2E5, was successfully incorporated into a nonaqueous gel for transdermal delivery. The thermal and rheological properties of a formulation containing 40% C2E5, 20% ethyl cellulose, and 40% Miglyol 840® prepared using the solvent evaporation method demonstrated that the gel had acceptable content uniformity and flow properties. In vitro studies showed that C2E5 was steadily released from the gel at a rate suitable for transdermal delivery. Topical application of the gel at a 200 mg C2E5/kg dose level in rats achieved significantly higher plasma exposures of several active metabolites compared with neat C2E5 oil at the same dose level. The results suggest that transdermal delivery of a chelator prodrug is an effective radionuclide decorporation strategy by delivering chelators to the circulation with a pharmacokinetic profile that is more consistent with the biokinetic profile of transuranic elements in contaminated individuals.
authors: Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, CB# 7362, 120 Mason Farm Rd, Chapel Hill, NC 27599-7362, USA.
authors: Yong
authors: Y
authors: Zhang
authors: Matthew P
authors: MP
authors: Sadgrove
authors: Katsuhiko
authors: K
authors: Sueda
authors: Yu-Tsai
authors: YT
authors: Yang
authors: Erik K
authors: EK
authors: Pacyniak
authors: John R
authors: JR
authors: Kagel
authors: Brenda A
authors: BA
authors: Braun
authors: William C
authors: WC
authors: Zamboni
authors: Russell J
authors: RJ
authors: Mumper
authors: Michael
authors: M
authors: Jay
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001711:Biotransformation; D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002614:Chelating Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004075:Diglycerides / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D005782:Gels; D004369:Pentetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012212:Rheology; D012869:Skin Absorption; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D002614:Chelating Agents; D003692:Delayed-Action Preparations; D004075:Diglycerides; D004337:Drug Carriers; D005782:Gels; D011355:Prodrugs; C583865:diethylenetriamine pentaacetic acid penta-ethyl ester; C079597:miglyol 840; D004369:Pentetic Acid; C013517:ethyl cellulose; D002482:Cellulose
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