Journal
JOURNAL OF COLLOID AND INTERFACE SCIENCE
Volume 338, Issue 1, Pages 56-62Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jcis.2009.05.025
Keywords
Dextran; Drug delivery; Polymer-drug conjugates; Nanoparticle; Ibuprofen
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The presented concept combines the widely-established use of macromolecular prodrugs with nanoparticulate drug delivery devices. For this purpose, the water-soluble biopolymer dextran was functionalized with poorly water-soluble drugs (ibuprofen, naproxen) via in situ activation of the carboxylic groups with N,N'-carbonyldiimidazole (CDI). The resulting hydrophobic derivatives self-assemble into nanoparticles with high loading efficiency during nanoprecipitation. The degree of substitution (DS) and the preparation technique strongly influence the size and the size distribution of the resulting nanoparticles. The particle suspensions remained stable over months in a pH value range between 4 and 11. Derivatives with high DS values are more stable against hydrolysis and after the addition of electrolytes than lowly substituted ones. Therefore, a defined tuning of the DS value may allow the adjustment of the pH-dependent hydrolysis rate and, hence, the release of the drugs. (C) 2009 Elsevier Inc. All rights reserved
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