期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 454, 期 1, 页码 559-561出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2013.06.058
关键词
Self-association; Aggregation; Doxorubicin; Permeation
资金
- European Commission for Research through the Marie Curie Initial Training Networks (FP7-PEOPLE-ITN) [237962]
For pharmaceutical scientists, it is important to know if dissolved drug molecules are present only as monomers or in the form of aggregates in a test solution or formulation. Amphiphilic or hydrophobic drugs frequently self-associate to form dimers, trimers or higher order aggregates. Doxorubicin aggregation was examined by a previously developed permeation technique to detect oligosaccharide aggregation in aqueous solutions. At very low doxorubicin concentrations dimers and trimers have been observed, but in aqueous 0.5 mg/ml doxorubicin solutions aggregates containing about 40 molecules were observed. The permeation studies were supported by TEM studies. The results indicate that neutral doxorubicin molecules aggregate more readily than the protonated ones. Doxorubicin aggregation is a stepwise process resulting in formation of aggregates of variable sizes are enhanced aggregation with increasing doxorubicin concentration. (c) 2013 Elsevier B.V. All rights reserved.
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