Abstract
For further increase of retention of doxorubicin (DOX) in tumor cells, we prepared the pegylated liposomes entrapping the complex of DOX with γ-cyclodextrin (γ-CyD) (complex-in-liposome), and then examined the physicochemical properties and the in vitro cellular uptake/release, compared with those of pegylated liposomes entrapping DOX alone (DOX-in-liposome). The particle sizes of these liposomes were almost comparable, and the entrapment ratios of both DOX and γ-CyD in liposomes were more than 90%. The release of DOX from liposomes in the fetal calf serum (FCS) was significantly inhibited by entrapment of γ-CyD in the liposomes. The cellular uptake of DOX into Colon-26 cells, a mouse rectal carcinoma cell line, after incubation with these liposomes was almost equivalent. However, the cellular release of DOX from cells in the complex-in-liposome system was markedly slower than that in the DOX-in-liposome system. These results suggest the potential use of liposomes containing the DOX/γ-CyD complex for high retention of DOX in tumor cells.
Similar content being viewed by others
Abbreviations
- complex-in-liposome:
-
pegylated liposomes entrapping the complex of doxorubicin with γ-cyclodextrin
- CH:
-
cholesterol
- CyD:
-
cyclodextrin
- DSPC:
-
distearoylphosphatidylcholine
- DSPE-PEG2000:
-
distearoylphosphatidylethanolamine-polyethylene glycol 2000
- DOX-in-liposome:
-
pegylated liposomes entrapping doxorubicin alone
- DOX:
-
doxorubicin
- EPR:
-
enhanced permeability and retention
- FCS:
-
fetal calf serum
- PEG:
-
polyethylene glycol
References
Uekama K., (2004) Chem. Pharm. Bull. 52: 900
Klibanov A.L., Maruyama K., Torchilin V.P., Huang L. (1990) FEBS Lett. 268: 235
Papahadjopoulos D., Allen T.M., Gabizon A., Mayhew E., Matthay K., Huang S.K., Lee K.D., Woodle M.C., Lasic D.D., Redemann C., Martin F.J. (1991) Proc. Natl. Acad. Sci. USA 88: 11460
Matsumura Y., Maeda H. (1986) Cancer Res. 46: 6387
Rose P.G. (2005) Oncologist 10: 205
Theodoulou M., Hudis C. (2004) Cancer 100: 2052
Xiong X.B., Huang Y., Lu W.L., Zhang H., Zhang X., Zhang Q. (2005) Pharm. Res. 22: 933
Forssen E., Willis M. (1998) Adv. Drug Deliv. Rev. 29: 249
McCormack B., Gregoriadis G. (1994) J. Drug Target. 2: 449
McCormack B., Gregoriadis G. (1994) Int. J. Pharm. 112: 249
Fatouros D.G., Hatzidimitriou K., Antimisiaris S.G. (2001) Eur. J. Pharm. Sci. 13: 287
Maestrelli F., Gonzalez-Rodriguez M.L., Rabasco A.M., Mura P. (2005) Int. J. Pharm. 298: 55
McCormack B., Gregoriadis G. (1996) Biochim. Biophys. Acta 1291: 237
Shew R.L., Deamer D.W. (1985) Biochim. Biophys. Acta 816: 1
Mayer L.D., Hope M.J., Cullis P.R. (1986) Biochim. Biophys. Acta 858: 161
Mayer L.D., Bally M.B., Cullis P.R. (1986) Biochim. Biophys. Acta 857: 123
Somani B.L., Khanade J., Sinha R. (1987) Anal. Biochem. 167: 327
Irie T., Uekama K. (1997) J. Pharm. Sci. 86: 147
Nishijo J., Mizuno H. (1998) Chem. Pharm. Bull. 46: 120
Bekers O., Beijnen J.H., Otagiri M., Bult A., Underberg W.J. (1990) J. Pharm. Biomed. Anal. 8: 671
Ono N., Arima H., Hirayama F., Uekama K. (2001) Biol. Pharm. Bull. 24: 395
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hagiwara, Y., Arima, H., Hirayama, F. et al. Prolonged Retention of Doxorubicin in Tumor Cells by Encapsulation of γ-Cyclodextrin Complex in Pegylated Liposomes. J Incl Phenom Macrocycl Chem 56, 65–68 (2006). https://doi.org/10.1007/s10847-006-9062-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10847-006-9062-9