Stealth liposomal doxorubicin

Working PK, Dayan AD. Pharmacological-toxicological expert report Caelyx (Stealth liposomal doxorubicin HCL). Hum Exp Tox 1996 15 752. 

Koukourakis, M. I., Koukouraki, S., Fezoulidis, I., Kelekis, N, Kyrias, G., Archimandritis, S., and Karkavitsas, N. (2000), High intratumoural accumulation of stealth liposomal doxorubicin (Caelyx) in glioblastomas and in metastatic brain tumors, Br. J. Cancer, 83, 1281-1286. 

Goebel FD, Goldstein D, Goos M, Jablonowski H, Stewart JS. Efficacy and safety of Stealth liposomal doxorubicin in AIDS-related Kaposi s sarcoma. The International SL-DOX Study Group. Br J Cancer 1996 73(8) 989-94. 

Rimassa L, Carnaghi C, Garassino I, Salvini P, Ginanni V, GuUo G et al (2003) Unexpected low efficacy of stealth liposomal doxorubicin (Caelyx) and vinorelbine in metastatic breast cancer. Breast Cancer Res Treat 77 185-188... 

Brouckaert P, Takahashi N, van Tiel S T, et al. (2004). Tumor necrosis factor-alpha augmented tumor response in B16BL6 melanoma-bearing mice treated with stealth liposomal doxorubicin (Doxil) correlates with altered Doxil pharmacokinetics. Int. J. Cancer. 109 442-448. 

Symon Z, Peyser A, Tzemach D, et al. Selective delivery of doxorubicin to patients with breast carcinoma metastases by Stealth liposomes. Cancer 1999 86 72-78. 

Sterically stabilized liposomal doxorubicin (pegylated liposomal doxorubicin Caelyx/Doxil) is coated with polyethylene glycol (3), which results in so-called stealth liposomes. In liposomal daunorubicin the liposome consists of a lipid bilayer of distearoylphosphati-dylcholine and cholesterol in a 2 1 molar ratio (4). Both formulations have a hydrophilic outer layer, which attracts a coating of water around the liposomal shell. This increases the circulation time by making the formulation virtually invisible to the reticuloendothelial system. 

PEGylated liposomal doxorubicin (DOXIL /Caelyx ) was the first and is still the only stealth liposome formulation to be approved in both USA and Europe for treatment of Kaposi s sarcoma (67) and recurrent ovarian cancer (68, 69). Currently, (DOXIL /Caelyx ) is undergoing trials for treatment of other malignancies such as multiple myelomas (70), breast cancer (71, 72), and recurrent high-grade glioma (73). 

Liposomes have emerged as efficient drug delivery systems for anticancer agents. A liposomal formulation of doxorubicin, Caelyx , is used in routine clinical use for cancer treatment (1,2). Compared with free doxorubicin, Caelyx provides preferred accumulation in tumors and consequently reduced side effects. Caelyx is a non-targeted stealth liposome formulation of encapsulated doxorubicin. Due to a long circulation half-life, Caelyx accumulates in tumors by the EPR (enhanced permeability and... 

Current opinion concerning the mechanism of delivery of liposomal therapeutics to tumors is that, once in the tumor, standard liposomes are localized in the extra-cellular fluid that surrounds the tumor cell but do not enter it i 8 ii Therefore, for delivery of the therapeutic agent, the drug must first be released into the extra-cellular fluid, from where it must then diffuse into the cell. There is the evidence that doxorubicin is released efficiently from Doxil liposomes, to be taken up by the cell in ovarian cancer and Kaposi s sarcoma. Concentrations of doxorubicin achieved in cells have been estimated as up to 13 times higher from Stealth liposomes than with a simple doxorubicin injection in patients undergoing treatment of Kaposi s sarcoma. hi contrast, evidence from the use of cisplatin seems less definitive. In studies comparing Stealth liposomal cisplatin (SPl-077) with standard cisplatin in... 

Working, P. K., Newman, M. S., Stuart, Y. Pharmacokinetics, bio distribution and therapeutic efficacy of doxorubicin encapsulated in STEALTH liposomes. J. Liposome Res. 1994, 46, 667-687. 

The consequences of liposome incorporation must be balanced. For example, loading of daunorubicin into conventional liposomes decreases the volume of distribution, increases peak concentration, and prolongs the initial rate of elimination from the plasma (Figure 8.14). The conventional liposomes are cleared from the circulation, however, producing a substantial drop in the plasma concentration of daunorubicin during the first 24 h after injection. In contrast, incorporation of doxorubicin into Stealth liposomes provides the... 

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