Plasma-Mediated Release of Morphine from Synthesized Prodrugs
Abstract
Two morphine prodrugs ( PDA and PDB ) were synthesized and the kinetics of esterase-mediated morphine release from these prodrugs were determined when incubated with plasma from different animal species. Morphine was rapidly released from PDA by all species' plasma with the maximum reached within 5-10 minutes; the released morphine was biologically active as determined by an in vitro cAMP assay. The morphine was released from PDB at a slower and species-dependent rate (mouse > rat > guinea pig > human). Morphine s release from PDB appeared to be mediated by carboxyl esterases as the release was inhibited by the carboxyl esterase inhibitor Benzil. PDA nor PDB induce cytotoxicity in the neuronal cell lines SK-NSH and SH-SY5Y. The carboxyl and amino functional moieties present on the linker portions of PDA and PDB, respectively, may facilitate their conjugation to nanoparticles to tailor morphine pharmacokinetics and specific targeting. These studies suggest the potential clinical utility of these prodrugs for morphine release at desired rates by administration of their mixture at selected ratios.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2013
- Accession Number
- ADA577469
Entities
People
- Abraham Van Der Spek
- Alina Kotlyar
- Ankur Desai
- Baohua Huang
- Brent B. Ward
- Hong Zong
- James R. Baker Jr.
- Pascale R. Leroueil
- Thomas Dunham
- Thommey P. Thomas
- Xue-min Cheng
Organizations
- University of Michigan