Biodegradable polymeric prodrugs of naltrexone

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Title Biodegradable polymeric prodrugs of naltrexone
Publication Type dissertation
School or College College of Pharmacy
Department Pharmaceutics & Pharmaceutical Chemistry
Author Bennett, David Bruce
Date 1990-03
Description Development of a polymeric naltrexone delivery system would give an effective means for treatment of opiate addiction. A novel approach involves synthesis and characterization of a biodegradable polymeric prodrug of naltrexone covalently coupled to poly(amino acids). Modification of the drug gave several prodrugs including: naltrexone-3-acetate (N3A), naltrexone-3,14-diacetate, naltrexone-14-acetate (N14A), and naltrexone-3-acetate-14-hemisuccinate (N3A14HS). Prodrugs were characterized by infrared and nuclear magnetic resonance spectroscopy. Hydrolysis rates of these esters were determined in phosphate buffer. Prodrugs were coupled via either ester or carbonate bonds to random copolymers of hydroxy-propyl-L-glutamine (HPG) with L-leucine (Leu) having compositions (HPG.-Leu) of 90:10, 80:20, 70:30, 60:40, and 50:50. Copolymers were synthesized by the base catalyzed polymerization of the amino acid N-carboxyanhydrides and had molecular weights between 45,000 and 100,000 as determined by viscometric analysis and wide-angle light scattering. In vitro studies showed rate and duration to be dependent upon copolymer composition, drug loading, covalent linkage type, and geometry of the devices. Subcutaneous injection of these polymeric prodrugs into rats as suspensions of particles led to plasma naltrexone levels that were relatively constant after exhibiting initial bursts. Conjugates of N3A and N14A directly bound to P(HPG50/Leu50) via carbonate bonds exhibited nearly constant naltrexone plasma levels for 1 month.
Type Text
Publisher University of Utah
Subject Therapeutic Use; Pharmacokinetics; Drug Therapy
Subject MESH Amino Acids; Drug Delivery Systems; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Polymers ;Prodrugs
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Biodegradable polymeric prodrugs of naltrexone Spencer S. Eccles Health Sciences Library.
Rights Management © David Bruce Bennett.
Format application/pdf
Format Medium application/pdf
Format Extent 2,412,396 bytes
Identifier undthes,4068
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available)
Master File Extent 2,412,511 bytes
ARK ark:/87278/s6ww7kdm
Setname ir_etd
ID 190506
Reference URL https://collections.lib.utah.edu/ark:/87278/s6ww7kdm
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