TY - JOUR
T1 - PEG liposomalization of paclitaxel improved its in vivo disposition and anti-tumor efficacy
AU - Yoshizawa, Yuta
AU - Kono, Yusuke
AU - Ogawara, Ken-ichi
AU - Kimura, Toshikiro
AU - Higaki, Kazutaka
N1 - Funding Information:
This research is supported in part by Grant-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science and Technology of Japan .
PY - 2011/6/30
Y1 - 2011/6/30
N2 - To find out potent paclitaxel (PTX) formulations for cancer chemotherapy, we formulated PTX in O/W emulsion and liposome selected as candidates of nanocarriers for PTX. Surface modification of these nanoparticles with polyethylene glycol (PEG) improved their in vivo behavior, but the effect of PEGylation on the pharmacokinetics of emulsion was not so remarkable and the release of PTX from emulsion was found to be very fast in blood circulation, indicating that emulsion would not be an adequate formulation for PTX. On the other hand, AUC of PEG liposome was 3.6 times higher than that of naked liposome after intravenous injection into normal rats due to the lower disposition into the reticuloendothelial system tissues such as liver and spleen. Since PEG liposome was able to stably encapsulate PTX in blood, AUC of PTX was also extensively enhanced after intravenous dosing of PTX-PEG liposome into normal rats. In the in vivo studies utilizing Colon-26 solid tumor-bearing mice, it was confirmed that PTX-PEG liposome delivered significantly larger amount of PTX to tumor tissue and provided more excellent anti-tumor effect than PTX-naked liposome. These results suggest that PEG liposome would serve as a potent PTX delivery vehicle for the future cancer chemotherapy.
AB - To find out potent paclitaxel (PTX) formulations for cancer chemotherapy, we formulated PTX in O/W emulsion and liposome selected as candidates of nanocarriers for PTX. Surface modification of these nanoparticles with polyethylene glycol (PEG) improved their in vivo behavior, but the effect of PEGylation on the pharmacokinetics of emulsion was not so remarkable and the release of PTX from emulsion was found to be very fast in blood circulation, indicating that emulsion would not be an adequate formulation for PTX. On the other hand, AUC of PEG liposome was 3.6 times higher than that of naked liposome after intravenous injection into normal rats due to the lower disposition into the reticuloendothelial system tissues such as liver and spleen. Since PEG liposome was able to stably encapsulate PTX in blood, AUC of PTX was also extensively enhanced after intravenous dosing of PTX-PEG liposome into normal rats. In the in vivo studies utilizing Colon-26 solid tumor-bearing mice, it was confirmed that PTX-PEG liposome delivered significantly larger amount of PTX to tumor tissue and provided more excellent anti-tumor effect than PTX-naked liposome. These results suggest that PEG liposome would serve as a potent PTX delivery vehicle for the future cancer chemotherapy.
KW - EPR effect
KW - PEG emulsion
KW - PEG liposome
KW - Paclitaxel
KW - Passive targeting
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U2 - 10.1016/j.ijpharm.2011.04.008
DO - 10.1016/j.ijpharm.2011.04.008
M3 - Article
C2 - 21507344
AN - SCOPUS:79957473802
VL - 412
SP - 132
EP - 141
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1-2
ER -
