TY - JOUR
T1 - Synthesis and characterization of redox-sensitive heparin-β-sitosterol micelles
T2 - Their application as carriers for the pharmaceutical agent, doxorubicin, and investigation of their antimetastatic activities in vitro
AU - Debele, Tilahun Ayane
AU - Mekuria, Shewaye Lakew
AU - Tsai, Hsieh Chih
N1 - Funding Information:
The authors would like to thank the Ministry of Science and Technology, Taiwan (MOST 103-2221-E-011-035) and the National Taiwan University of Science and Technology (105H451714) for providing financial support.
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Although there are several clinical attempts to treat tumors at the primary site, only few therapies can inhibit the spread of metastatic cancers. In this study, we synthesized redox-sensitive heparin-β-sitosterol micelles that show antimetastatic activity. Proton nuclear magnetic resonance and Fourier transform infrared analyses confirmed the formation of bioreducible heparin-β-sitosterol (bHSC) conjugates, whereas dynamic light scattering was used to measure the particle size and zeta potential. Both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assays confirmed the low toxicity of the synthesized micelles. Doxorubicin (Dox) was encapsulated via the dialysis method, and its loading and encapsulation efficiencies were 16.49 ± 1.2% and 58.47 ± 1.87%, respectively. An in vitro release study showed that approximately 89% and 52% of Dox were released after 48 h in the presence and absence of reduced glutathione, respectively. The hemocompatibility and antimetastatic effects of bHSC were evaluated using the hemolysis and scratch assays, respectively. F-Actin fluorescence microscopy showed that heparin- and bHSC-treated HeLa cells had poorly oriented stress fibers. In summary, the synthesized bHSC micelles are good candidates as drug delivery systems owing to their low toxicity, excellent hemocompatibility, and antimetastatic effects.
AB - Although there are several clinical attempts to treat tumors at the primary site, only few therapies can inhibit the spread of metastatic cancers. In this study, we synthesized redox-sensitive heparin-β-sitosterol micelles that show antimetastatic activity. Proton nuclear magnetic resonance and Fourier transform infrared analyses confirmed the formation of bioreducible heparin-β-sitosterol (bHSC) conjugates, whereas dynamic light scattering was used to measure the particle size and zeta potential. Both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assays confirmed the low toxicity of the synthesized micelles. Doxorubicin (Dox) was encapsulated via the dialysis method, and its loading and encapsulation efficiencies were 16.49 ± 1.2% and 58.47 ± 1.87%, respectively. An in vitro release study showed that approximately 89% and 52% of Dox were released after 48 h in the presence and absence of reduced glutathione, respectively. The hemocompatibility and antimetastatic effects of bHSC were evaluated using the hemolysis and scratch assays, respectively. F-Actin fluorescence microscopy showed that heparin- and bHSC-treated HeLa cells had poorly oriented stress fibers. In summary, the synthesized bHSC micelles are good candidates as drug delivery systems owing to their low toxicity, excellent hemocompatibility, and antimetastatic effects.
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U2 - 10.1016/j.msec.2017.03.052
DO - 10.1016/j.msec.2017.03.052
M3 - Article
C2 - 28415422
AN - SCOPUS:85015377397
SN - 0928-4931
VL - 75
SP - 1326
EP - 1338
JO - Materials Science and Engineering C
JF - Materials Science and Engineering C
ER -