Doxil liposome

Pegulated liposomal doxorubicin (Doxil) Liposome encapsulated doxorubicin Ovarian Phase II data... 

Liposomal formulations, type of tumor, anticancer agent, delivery pathway, day of treatment, and general conclusions are given in Table 6. DaunoXome (liposomal daunorubicin) and Doxil (liposomal doxorubicin) have been proved to have good response in clinical trials, in the range of approximately 40%. 

Doxil - liposomal doxorubicin Navelbine - vinorelbine tartrate Uromitexan - mesna... 

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... 

Doxil Liposome Doxorubicin Passive Breast, ovarian FDA approved " ... 

Several liposome-based drugs have been approved for clinical application [64]. One of the clinically approved liposomes is Doxil, a PEGylated liposome containing doxorubicin (DOX), which is used for the treatment of a number of diseases [65]. As shown in this case, in the field of liposome drug development, PEG is widely used to protect the liposome from recognition by opsonins, thereby reducing liposome clearance. 

Amphipathic Weak Base Loading into Preformed Liposomes Having a Transmembrane Ammonium Ion Gradient From the Bench to Approved Doxil... 

Doxil, the first liposomal drug that was approved by the Food and Drug Administration, in 1995, is a good example of the successful application of a transmembrane inner liposome high/outer liposome low ammonium ion gradient for remote loading of an amphipathic weak base, the anticancer... 

THE DOXIL EXAMPLE FOR REMOTE LOADING OF AMPHIPATHIC WEAK BASE INTO LIPOSOMES... 

The octanol/buffer represents a partition coefficient between two bulk phases it is less affected by the structure of the analyte and therefore it cannot be used to predict the exact value of liposome membrane-to-buffer Xp, which is also affected by the geometry of the analyte (41 4). However, it is accepted and established that the octanol-to-buffer can help to predict transmembrane passive diffusion (40). In the case of liposomes such as Doxil, in which the internal aqueous phase (intraliposome aqueous phase) is different from the external liposome aqueous medium due to large differences in the composition and pH of these two aqueous phases, there are two different liposome membrane-to-aqueous phase partition coefficients this is referred to as asymmetry in the membrane-to-aqueous media partition coefficient. 

Judson I, Radford JA, Harris M, et al. Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL(R)/CAELYX(R)) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma, a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2001 37 870. 

Chanan-Khan A, Szebeni J, Savay S, et al. Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil) possible role in hypersensitivity reactions. Ann Oncol 2003 14 1430. 

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. 

Bao A, Goins B, Klipper R, Negrete G, Phillips WT. Direct Tc labeling of pegylated liposomal doxorubicin (Doxil) for pharmacokinetic and non-invasive imaging studies. J Pharmacol Exp Ther 2004 308 419. 

Skubitz KM. Phase II trial of pegylated-liposomal doxirubicin (Doxil) in sarcoma. Cancer Investig 2003 21 167. 

Szebeni J, Baranyi L, Savay S, et al. Role of complement activation in hypersensitivity reactions to doxil and hynic PEG liposomes experimental and clinical studies. J Liposome Res 2002 12 165. 

In September 2007, the EMEA approved the use of trabectidin against ovarian cancer (OC) and STS. In November 2009, Yondelis received its second marketing authorization from the European Commission for its administration in combination with pegylated liposomal doxorubicin (Doxil, Caelyx) for the treatment of women with relapsed ovarian cancer presently, trabectedin (36) is under Phase II trials for the treatment of paediatric sarcomas as well as breast and prostate cancers. The European Commission and the US Food and Drug Administration (FDA) have granted orphan drug status to trabectedin for soft tissue sarcomas and... 

Also known as Doxil PEG-coated liposome formulation with doxorubicin. 

There are three liposomal forms of doxorubicin or daunorubicin on the market (Table 8.6). Doxil and DaunoXome have been approved for the treatment of AIDS-related Kaposi s sarcoma and are being evaluated in clinical trials for the treatment of a variety of cancers [148-151]. Evacet (liposomal doxorubicin) has recently been tested in large phase II and III clinical trials for the treatment of metastatic breast cancer and is awaiting approval by the FDA [151], Data obtained from trials thus far suggest that all three liposomal drugs offer significant therapeutic benefit compared with the free drug [113]. 

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