Polyethylene liposomal doxorubicin

Coukell AJ, Spencer CM. Polyethylene glycol-liposomal doxorubicin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the management of AIDS-related Kaposi s sarcoma. Drugs 1997 53 520. 

Cabanes, A., Even-Chen, S., Zimberoff, J., Barenholz, Y., Kedar, E., and Gabizon, A. (1999), Enhancement of antitumor activity of polyethylene glycol-coated liposomal doxorubicin with soluble and liposomal interleukin 2, Clini. Cancer Res., 5, 687-693. 

Godfredsen, C.F. Van Berkel, Th.J.C. Kruijt, J.K. Goethais, A. Biochem. Pharmacol 1983, 32, 3389-3396. Gabizon, A. Martin, F. Polyethylene glycol-coated (pegy-lated) liposomal doxorubicin. Rationale for use in solid tumours. Drugs 1997, 54, 15-21. 

In 60 patients receiving polyethylene glycol-coated liposomal doxorubicin (Doxil) 35-70 mg/m by infusion over 1-2 hours there were four patterns of skin eruption hand-foot syndrome (40%), a diffuse follicular rash (10%), an intertrigo-like eruption (8%), and new melanotic macules (0.5%) (81). 

Lotem M, Hubert A, Lyass O, Goldenhersh MA, Ingber A, Peretz T, Gabizon A. Skin toxic effects of polyethylene glycol-coated liposomal doxorubicin. Arch Dermatol 2000 136(12) 1475-80. 

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. 

Gabizon A, Martin F. Polyethylene glycol-coated (pegy-lated) liposomal doxorubicin. Rationale for use in solid tumours. Drugs 1997 54(Suppl 4) 15-21. 

Cady FM, Kneuper-Hall R, Metcalf JS (2006) Histologic patterns of polyethylene glycol-liposomal doxorubicin-related cutaneous eruptions. Am J Dermatopathol 28 168-172... 

Gabizon A, Catane R, Uziely B, et al. Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer Res 1994 54 987-992. 

Gabizon AA, Barenholz Y, Bialer M. Prolongation of the circulation time of doxorubicin encapsulated in liposomes containing polyethylene glycol-derivatized phospholipid pharmacokinetic studies in rodents and dogs. Pharm Res 1993 10(5) 703. 

Recently, this method was adapted to label two commercially available liposomal formulations doxorubicin encapsulated in polyethylene glycol (PEG)-coated liposomes (Caelyx /Doxil ) (14) and daunorubicin encapsulated in small distearoyl-phosphatidyl-choline/cholesterol liposomes (Daunoxome ) (15). Although no DTPA was encapsulated in these liposomes, the labeling efficiency was typically between 70% and 80% and the radiolabeled preparations were stable in vivo during the time course of the experiment (four hours). Most likely, the lipophilic In-oxine avidly associates with the lipid bilayer and encapsulation of DTPA might not be necessary when the experimental observation period does not exceed four to six hours. 

Northfelt DW, Martin FJ, Working P, Volberding PA, Russell J, Newman M, Amantea MA, Kaplan LD. Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi s sarcoma. J Clin Pharmacol 1996 36 55-63. 

Then, there are liquid crystalline drug delivery systems (DDS). Anticancer drugs that enclose the water-soluble doxorubicin hydrochloride in a bilayer membrane phospholipid liposomes modified with polyethylene glycol [205] were approved in Japan in 2007. 

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