Abstract
Dextrin is a biomedically well-established, water-soluble polymer that has recently attracted considerable interest for conjugation to bioactive payloads. Succinoylation functionalizes dextrin and alters the rate at which it is degraded by human amylase, providing the bases for a convenient, controlled drug release technology. To date, the choice of a succinoylated dextrin intermediate requires laborious physicochemical characterization of entire libraries of succinoylated dextrin intermediates. We report the governance of dextrin degradation as a function of initial polymer molecular weight and degree of succinoylation through statistical analysis of a library of succinoylated dextrins relevant to acute disease (parent-dextrin molecular weight: 8,100 to 28,900 g/mol; 0 to 14.5 mol% succinoylation) at a typical physiologic concentration of human amylase (100 IU/L). Within these parameters, the rate of degradation of all succinoylated dextrins was best predicted by logarithmic regression. The contribution of degree of succinoylation to the variance in the degradation rate increased progressively and substantially with decreasing initial polymer weight (4.19% to 21.33%). These results facilitate the choice of succinoylated dextrin intermediates in the construction of controlled-release constructs, increase relevance to clinical scenarios requiring specific controlled-release rates, and contribute to the adoption of succinoylated dextrin as a versatile polymer for conjugation in controlled-release therapeutics.
ACKNOWLEDGMENTS
Work from this manuscript has been presented at the Society for Academic Research Surgery, Royal Society of Medicine, London, 2013. (Recipient, Jackson Award for Burn Surgery Research.)
The authors would like to thank Dr. Koenrad Beck (Cardiff University) for his assistance and helpful discussions. The research work disclosed in this publication is partially funded by the Strategic Educational Pathways Scholarship (Malta). The scholarship is part-financed by the European Union.