TY - JOUR
T1 - Liposomal co-delivery of omacetaxine mepesuccinate and doxorubicin for synergistic potentiation of antitumor activity
AU - Shim, Gayong
AU - Lee, Sangbin
AU - Choi, Junhyeok
AU - Lee, Soondong
AU - Kim, Chan Wha
AU - Oh, Yu Kyoung
N1 - Funding Information:
Gayong Shim and Sangbin Lee contributed equally to this work. This work was supported by research grants from the Ministry of Science, ICT and Future Planning (No. 2013035166; 2013036131), from the Korean Health Technology R&D project, Ministry of Health and Welfare (No. A092010), and from Business for Cooperative R&D between Industry, Academy, and Research Institute funded Korea Small and Medium Business Administration (No. C0010962).
Publisher Copyright:
© 2014 Springer Science+Business Media New York.
PY - 2014/8
Y1 - 2014/8
N2 - Purpose: Anticancer chemotherapy usually involves the administration of several anticancer drugs that differ in their action mechanisms. Here, we aimed to test whether the combination of omacetaxine mepesuccinate (OMT) and doxorubicin (DOX) could show synergism, and whether the liposomal co-delivery of these two drugs could enhance their antitumor effects in cervical carcinoma model.Method: OMT-loaded liposomes (OL) were prepared by loading the drug in the lipid bilayers. OL were then electrostatically complexed with DOX, yielding double-loaded liposomes (DOL). DOX-loaded liposomes (DL) were formulated by electrostatic interaction with negatively charged empty liposomes (EL). The combination index (CI) values were calculated to evaluate the synergism of two drugs. In vitro antitumor effects against HeLa cells were measured using CCK-8, calcein staining, and crystal violet staining. In vivo antitumor effects of various liposomes were tested using HeLa cell-bearing mice.Results: Combination of DOX and OMT had ratio-dependent synergistic activities, with very strong synergism observed at a molar ratio of 4:1 (DOX:OMT). The sizes of EL, DL, OL, and DOL did not significantly differ, but the zeta potentials of DL and DOL were slightly higher than those of OL and EL. In vitro, DOL showed higher antitumor activity than OL, DL or EL in cervical carcinoma HeLa cells. In vivo, unlike other liposomes, DOL reduced the tumor growths by 98.6% and 97.3% relative to the untreated control on day 15 and 25 after the cessation of treatment, respectively.Conclusions: These results suggest that liposomal co-delivery of DOX and OMT could synergistically potentiate antitumor effects.
AB - Purpose: Anticancer chemotherapy usually involves the administration of several anticancer drugs that differ in their action mechanisms. Here, we aimed to test whether the combination of omacetaxine mepesuccinate (OMT) and doxorubicin (DOX) could show synergism, and whether the liposomal co-delivery of these two drugs could enhance their antitumor effects in cervical carcinoma model.Method: OMT-loaded liposomes (OL) were prepared by loading the drug in the lipid bilayers. OL were then electrostatically complexed with DOX, yielding double-loaded liposomes (DOL). DOX-loaded liposomes (DL) were formulated by electrostatic interaction with negatively charged empty liposomes (EL). The combination index (CI) values were calculated to evaluate the synergism of two drugs. In vitro antitumor effects against HeLa cells were measured using CCK-8, calcein staining, and crystal violet staining. In vivo antitumor effects of various liposomes were tested using HeLa cell-bearing mice.Results: Combination of DOX and OMT had ratio-dependent synergistic activities, with very strong synergism observed at a molar ratio of 4:1 (DOX:OMT). The sizes of EL, DL, OL, and DOL did not significantly differ, but the zeta potentials of DL and DOL were slightly higher than those of OL and EL. In vitro, DOL showed higher antitumor activity than OL, DL or EL in cervical carcinoma HeLa cells. In vivo, unlike other liposomes, DOL reduced the tumor growths by 98.6% and 97.3% relative to the untreated control on day 15 and 25 after the cessation of treatment, respectively.Conclusions: These results suggest that liposomal co-delivery of DOX and OMT could synergistically potentiate antitumor effects.
KW - antitumor effects
KW - co-delivery
KW - combination therapy
KW - liposomes
KW - omacetaxine mepesuccinate
UR - http://www.scopus.com/inward/record.url?scp=84894092507&partnerID=8YFLogxK
U2 - 10.1007/s11095-014-1317-3
DO - 10.1007/s11095-014-1317-3
M3 - Article
C2 - 24562810
AN - SCOPUS:84894092507
SN - 0724-8741
VL - 31
SP - 2178
EP - 2185
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 8
ER -