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ORIGINAL RESEARCH ARTICLE

Doxorubicin and ß-Lapachone Release and Interaction with Micellar Core Materials: Experiment and Modeling

Damon Sutton^*,, Shihu Wang, Norased Nasongkla^*,,1, Jinming Gao^* and Elena E. Dormidontova^,2

^* Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390; and Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, Ohio 44106

To whom requests for reprints should be addressed at ² Department of Macromolecular Science and Engineering, Case Western Reserve University, 2100 Adelbert Road, Cleveland, OH 44106. E-mail: eed{at}case.edu

Polymer micelles with two different core-forming blocks, poly(D,L -lactide) (PLA) and poly(-caprolactone) (PCL), but the same coronal material, poly(ethylene glycol) (PEG), were investigated in this study as nanoscopic drug carriers. The release of two different drugs, doxorubicin (DOX) and ß-lapachone (ß-lap), from PEG(5k)-b-PCL(5k) and PEG(5k)-b-PLA(5k) micelles was studied at pH 5.0 and 7.4. Mathematical solutions of both Higuchi’s model and Fickian diffusion equations were utilized to elucidate the differences between the micelle core materials for the two drugs. The neutral and smaller of the two drugs tested, ß-lap, demonstrated faster, pH-independent release, suggesting that no substantial changes occurred in either micelle core at lower pH. In contrast, the release rate of DOX was found to noticeably increase at lower pH with a larger cumulative amount of drug released. Different core materials were shown to have considerable influence on the release kinetics of both drugs: in both cases, the more hydrophobic PCL core showed slower drug release rates compared with the less hydrophobic PLA core.

Key Words: polymer micelles • drug release • drug-polymer interactions • mathematical modeling • physicochemical properties