Abstract
To elucidate the determinants of the in vivo anti-tumor efficacy of polyethylene glycol (PEG)-modified liposomal doxorubicin (DOX), we examined its anti-tumor effect against three different tumor cell lines (Lewis lung cancer (LLC), Colon-26 (C26) and B16BL6 melanoma (B16)) in vitro and in vivo. In vitro, LLC was the most sensitive tumor to DOX and liposomal DOX based on the MTT assay. However, the strongest in vivo anti-tumor effect was observed in the C26 tumor-bearing mice. The in vivo accumulation of radiolabelled PEG liposome in the C26 tumor after intravenous injection was significantly larger than in other tumors. The extent of vascularity assessed by immunohistochemical staining of CD31 was not directly related with the tumor accumulation of PEG liposome. On the other hand, Evans blue extravasation and secretion of VEGF in C26 tumors were higher than in LLC tumors, clearly demonstrating that the vasculature permeability was higher within C26 tumors. These results indicated that the vascular permeability within the tumor substantially affects the tumor accumulation of PEG liposome and may be one of the important determinants in the in vivo anti-tumor efficacy of PEG liposomal DOX.
| Original language | English |
|---|---|
| Pages (from-to) | 234-240 |
| Number of pages | 7 |
| Journal | International Journal of Pharmaceutics |
| Volume | 359 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - Jul 9 2008 |
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Keywords
- Doxorubicin
- EPR effect
- Liposome
- Tumor vasculature
- VEGF
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Determinants for in vivo anti-tumor effects of PEG liposomal doxorubicin : Importance of vascular permeability within tumors. / Ogawara, Ken ichi; Un, Keita; Minato, Keiko; Tanaka, Ken ichi; Higaki, Kazutaka; Kimura, Toshikiro.
In: International Journal of Pharmaceutics, Vol. 359, No. 1-2, 09.07.2008, p. 234-240.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Determinants for in vivo anti-tumor effects of PEG liposomal doxorubicin
T2 - Importance of vascular permeability within tumors
AU - Ogawara, Ken ichi
AU - Un, Keita
AU - Minato, Keiko
AU - Tanaka, Ken ichi
AU - Higaki, Kazutaka
AU - Kimura, Toshikiro
PY - 2008/7/9
Y1 - 2008/7/9
N2 - To elucidate the determinants of the in vivo anti-tumor efficacy of polyethylene glycol (PEG)-modified liposomal doxorubicin (DOX), we examined its anti-tumor effect against three different tumor cell lines (Lewis lung cancer (LLC), Colon-26 (C26) and B16BL6 melanoma (B16)) in vitro and in vivo. In vitro, LLC was the most sensitive tumor to DOX and liposomal DOX based on the MTT assay. However, the strongest in vivo anti-tumor effect was observed in the C26 tumor-bearing mice. The in vivo accumulation of radiolabelled PEG liposome in the C26 tumor after intravenous injection was significantly larger than in other tumors. The extent of vascularity assessed by immunohistochemical staining of CD31 was not directly related with the tumor accumulation of PEG liposome. On the other hand, Evans blue extravasation and secretion of VEGF in C26 tumors were higher than in LLC tumors, clearly demonstrating that the vasculature permeability was higher within C26 tumors. These results indicated that the vascular permeability within the tumor substantially affects the tumor accumulation of PEG liposome and may be one of the important determinants in the in vivo anti-tumor efficacy of PEG liposomal DOX.
AB - To elucidate the determinants of the in vivo anti-tumor efficacy of polyethylene glycol (PEG)-modified liposomal doxorubicin (DOX), we examined its anti-tumor effect against three different tumor cell lines (Lewis lung cancer (LLC), Colon-26 (C26) and B16BL6 melanoma (B16)) in vitro and in vivo. In vitro, LLC was the most sensitive tumor to DOX and liposomal DOX based on the MTT assay. However, the strongest in vivo anti-tumor effect was observed in the C26 tumor-bearing mice. The in vivo accumulation of radiolabelled PEG liposome in the C26 tumor after intravenous injection was significantly larger than in other tumors. The extent of vascularity assessed by immunohistochemical staining of CD31 was not directly related with the tumor accumulation of PEG liposome. On the other hand, Evans blue extravasation and secretion of VEGF in C26 tumors were higher than in LLC tumors, clearly demonstrating that the vasculature permeability was higher within C26 tumors. These results indicated that the vascular permeability within the tumor substantially affects the tumor accumulation of PEG liposome and may be one of the important determinants in the in vivo anti-tumor efficacy of PEG liposomal DOX.
KW - Doxorubicin
KW - EPR effect
KW - Liposome
KW - Tumor vasculature
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=44749086570&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44749086570&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2008.03.025
DO - 10.1016/j.ijpharm.2008.03.025
M3 - Article
VL - 359
SP - 234
EP - 240
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1-2
ER -