TY - JOUR
T1 - Doxorubicin and β-lapachone release and interaction with micellar core materials
T2 - Experiment and modeling
AU - Sutton, Damon
AU - Wang, Shihu
AU - Nasongkla, Norased
AU - Gao, Jinming
AU - Dormidontova, Elena E.
N1 - Funding Information:
This work was supported by grants R21CA112436 (E.E.D.) and RO1CA90696 (J.G.) from the National Institutes of Health.
PY - 2007/9
Y1 - 2007/9
N2 - Polymer micelles with two different core-forming blocks, poly(D,L-lactide) (PLA) and poly(ε-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 β-lapachone (β-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, β-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.
AB - Polymer micelles with two different core-forming blocks, poly(D,L-lactide) (PLA) and poly(ε-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 β-lapachone (β-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, β-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.
KW - Drug release
KW - Drug-polymer interactions
KW - Mathematical modeling
KW - Physicochemical properties
KW - Polymer micelles
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U2 - 10.3181/0702-RM-31
DO - 10.3181/0702-RM-31
M3 - Article
C2 - 17720955
AN - SCOPUS:34548462205
SN - 1535-3702
VL - 232
SP - 1090
EP - 1099
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
IS - 8
ER -