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Specific‐enzyme release of cellulose‐bound drugs, experimental and theoretical study
Author(s) -
Lapicque F.,
Dellacherie E.
Publication year - 1986
Publication title -
journal of applied polymer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.575
H-Index - 166
eISSN - 1097-4628
pISSN - 0021-8995
DOI - 10.1002/app.1986.070320101
Subject(s) - hydrolysis , chemistry , prodrug , denaturation (fissile materials) , cellulose , adsorption , substrate (aquarium) , chymotrypsin , reaction rate constant , organic chemistry , catalysis , immobilized enzyme , polymer , enzyme , polymer chemistry , kinetics , nuclear chemistry , trypsin , biochemistry , oceanography , physics , quantum mechanics , geology
Various polymeric prodrugs of pholcodine were prepared by covalently linking a substrate ester of the hydroxylic drug to cellulosic derivatives. The ester derivatives of the drug were chosen so that the resulting insoluble cellulosic prodrugs became substrates of α‐chymotrypsin. The hydrolysis of such compounds was studied for various spacer arms in conditions simulating the intestinal medium. A theoretical model was developed to describe the enzymatic catalysis of this hydrolysis, taking into account the adsorption of the enzyme onto the polymer, the hydrolysis reaction, and the enzyme denaturation. The resulting equations using independently determined parameter values such as the Langmuir adsorption constants, the enzyme denaturation constants, and the initial hydrolysis rate constant successfully correlated with the experimental data.