In Vitro and In Vivo Evaluations of Dihydroquinoline- and Dihydroisoquinoline-based Targetor Moieties for Brain-specific Chemical Delivery Systems

• Published in: Journal of drug targeting Vol. 10; no. 1; pp. 63 - 71
• Main Authors: Bodor, Nicholas, Farag, Hassan H., Barros, M. Dulce C., Wu, Whei-Mei, Buchwald, Peter
• Format: Journal Article
• Language: English
• Published: Abington Informa UK Ltd 01.02.2002; Taylor & Francis
• Subjects: Animals; Biological and medical sciences; Brain - metabolism; Brain-targeted Delivery; Chromatography, High Pressure Liquid; Dihydropyridine; Drug Delivery Systems; Drug Stability; Ferricyanides; General pharmacology; Hydrocortisone; Hydrocortisone - administration & dosage; Hydrocortisone - pharmacokinetics; Hydrogen Peroxide; Indicators and Reagents; Isoquinolines - chemistry; Kinetics; Male; Medical sciences; Oxidants; Oxidation-Reduction; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Quinolines - chemistry; Rats; Rats, Sprague-Dawley; Redox; Silver Nitrate; Testosterone; Testosterone - administration & dosage; Testosterone - pharmacokinetics; Tissue Distribution; Intravenous administration; Targeting; Rat; Central nervous system; Hydrocortisone; Ester; Dihydropyridine derivatives; Oxidation; Chemical synthesis; Corticosteroid; Isoquinoline derivatives; Stability; Pharmaceutical technology; Hydration; Rodentia; Quinoline derivatives; In vitro; In vivo; Testosterone; Vertebrata; Mammalia; Animal; Organic amide; Physicochemical properties; Brain (vertebrata)
• ISSN: 1061-186X; 1029-2330
• DOI: 10.1080/10611860290007540

Brain-targeted delivery of various drugs can be successfully achieved by chemical delivery systems (CDS) that contain a 1,4-dihydropyridine-based redox targetor moiety and undergo a sequential metabolism. However, the susceptibility of this moiety toward hydration in acidic media may limit the shelf-life of such compounds in aqueous formulation. Here, a systematic investigation of the chemical stability toward oxidation and hydration of ester and amide derivatives of 3-substituted 1,4-dihydropyridine, 1,4-dihydroquinoline, and 4-substituted 1,2-dihydroisoquinoline is reported, together with the in vitro stability and in vivo (rat) distribution of isoquinoline-based testosterone and hydrocortisone chemical delivery systems, which were selected as having the most suitable acid-resistant targetor moieties.