DOXIL®, doxorubicin

Neopharm LED doxorubicin Inex onco TCS vincristine Neopharm LEP paclitaxel Elan inyocet doxorubicin Gilead ambisome amphoteracin Gilead daunXome daunorubicin Alza doxil doxorubicin QLT visudyn verteporfin... 

Doxil (doxorubicin HC1 liposome injection, 2 mg/mL) from Ortho Biotech. 

Dezube BJ. Safety assessment Doxil (doxorubicin HCl liposome injection) in refractory AIDS-related Kaposi s sarcoma. Doxil Clinical Series, Vol. 1, No. 2. Menlo Park, California SEQUUS Pharmaceuticals Inc, 1996. 

Doxil (doxorubicin) an anticancer drug for the treatment of metastatic ovarian cancer in patients with disease that is refractory to both paclitaxel-and platinum-based chemotherapy regimens and for the treatment of AIDS-related Kaposi s sarcoma with disease that has progressed. 

Liposomes are lipid-based vesicles useful in delivering conventional as well as macromolecular therapeutic agents (35). The commercially available liposomal formulations include Doxil (doxorubicin) and Ambisome (amphotericin B), which are available for the treatment of tumors and fungal infections, respectively. Egg yolk and soy lecithins that are mainly composed of phospholipids (< 95%) are commonly used as raw materials for liposome preparation. Of the two, soy lecithins are generally preferred for reasons of... 

Janssen products L. Doxil (doxorubicin hydrochloride) injection, suspension, liposomal. 2014. [04.04.14]. Available from http //dailymed.nlm.nih.gov/dailymed/lookup.cfin setid=21d9c619-7e94-49e2-ac41-31e9ea96554a. 

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. 

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

Doxil , of which I had the pleasure of being one of the inventors (1-12), serves as an example of successful passive targeting to tumors in animals and humans (1,3,4,13). The ammonium sulfate (AS) transmembrane inside high/outside low gradient-driven loading is also the basis for doxorubicin (DOX) loading for Targeted Doxil (14), which soon will be tested in clinical trials. 

Removal of nonentrapped doxorubicin (in the case of Doxil this step was omitted as loading is approaching 100%)... 

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. 

Figure 3 Planar scintigraphic images acquired at various times of a normal rat intravenously injected with Tc-Doxil (17MBq) Tc, 2 mg doxorubicin, and 16 mg total lipid labeled using Tc-iV,iV-bis(2-mercaptoethyl)-Af, Af diethyl-ethylenediamine method. Abbreviations-. H, heart L, liver K, kidney B, bowel.

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. 

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]. 

Doxorubicin Doxil (Caelyx) Alza-corporation AIDS-related Kaposi s sarcoma... 

For insertion into premade doxorubicin-loaded liposomes (Doxil), mix equal volumes of liposomes and lipidation reaction mixture and incubate at 37°C for 12-16 h (see Note 7). Purification of unreacted lipid and protein is not necessary at this step, because they do not interfere with insertion process and will be removed eventually by gel-filtration of decorated liposomes on Sepharose CL-4B. 

Long circulating liposomes can exploit the EPR effect to accumulate at sites where pathological reactions occur. For example, the commercial product Doxil (marketed as Caelyx in Europe) consists of smallsized PEGylated liposomes, encapsulating the cytostatic doxorubicin. The resulting long circulation times and small size of the vesicles facilitate their accumulation in tumor tissue via the EPR effect. 

Doxorubicin Mycet Doxil/Caelyx Breast cancer Sarcoma, ovarian cancer, breast cancer... 

Daunorabicin (DaunoXome, Gilead Sciences, Inc.) Doxorubicin (Doxil/Caelyx, Ortho Biotech ProductsLP/Sequus Pharmaceuticals) Amphotericin B (Ambisome/Abelcet, Fujisawa Healthcare, Wyeth Pharmaceuticals) Doxorubicin (Myocet/Evacet, Sopherion/ Liposome Company) Hepatitis A virus envelope proteins (Epaxal, Berna Biotech) Influenza virus (Inflexal V, Berna Biotech) Verteporfin (Visudyne, Novartis Ophthalmics) Kaposi s sarcoma Kaposi s sarcoma Fungal infections in immunocompromised patients Metastatic breast cancer Hepatitis A Influenza Age-related macular degeneration... 

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%. 

In phase I clinical trials children with recurrent or refractory tumors previously treated with free doxorubicin were administered i.v. Doxil in various doses (40-70mg/m2) in order to determine the best tolerated one [391], It was concluded that the maximum tolerated dose was 60mg/m2 because at the highest, 70mg/m2, some patients developed mucositis, so dose adjustment was necessary. 

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