From Conventional to Stealth Liposomes a new Frontier in Cancer Chemotherapy
Tóm tắt
Many attempts have been made to achieve good selectivity to targeted tumor cells by preparing specialized carrier agents that are therapeutically profitable for anticancer therapy. Among these, liposomes are the most studied colloidal particles thus far applied in medicine and in particular in antitumor therapy. Although they were first described in the 1960s, only at the beginning of 1990s did the first therapeutic liposomes appear on the market. The first-generation liposomes (conventional liposomes) comprised a liposome-containing amphotericin B, Ambisome (Nexstar, Boulder, CO, USA), used as an antifungal drug, and Myocet (Elan Pharma Int, Princeton, NJ, USA), a doxorubicin-containing liposome, used in clinical trials to treat metastatic breast cancer. The second-generation liposomes (“pure lipid approach”) were long-circulating liposomes, such as Daunoxome, a daunorubicin-containing liposome approved in the US and Europe to treat AIDS-related Kaposi's sarcoma. The third-generation liposomes were surface-modified liposomes with gangliosides or sialic acid, which can evade the immune system responsible for removing liposomes from circulation. The fourth-generation liposomes, pegylated liposomal doxorubicin, were called “stealth liposomes” because of their ability to evade interception by the immune system, in the same way as the stealth bomber was able to evade radar. Actually, the only stealth liposome on the market is Caelyx/Doxil (Schering-Plough, Madison NJ, USA), used to cure AIDS-related Kaposi's sarcoma, resistant ovarian cancer and metastatic breast cancer. Pegylated liposomal doxorubicin is characterized by a very long-circulation half-life, favorable pharmacokinetic behavior and specific accumulation in tumor tissues. These features account for the much lower toxicity shown by Caelyx in comparison to free doxorubicin, in terms of cardiotoxicity, vesicant effects, nausea, vomiting and alopecia. Pegylated liposomal doxorubicin also appeared to be less myelotoxic than doxorubicin. Typical forms of toxicity associated to it are acute infusion reaction, mucositis and palmar plantar erythrodysesthesia, which occur especially at high doses or short dosing intervals. Active and cell targeted liposomes can be obtained by attaching some antigen-directed monoclonal antibodies (Moab or Moab fragments) or small proteins and molecules (folate, epidermal growth factor, transferrin) to the distal end of polyethylene glycol in pegylated liposomal doxorubicin. The most promising therapeutic application of liposomes is as non-viral vector agents in gene therapy, characterized by the use of cationic phospholipids complexed with the negatively charged DNA plasmid. The use of liposome formulations in local-regional anticancer therapy is also discussed. Finally, pegylated liposomal doxorubicin containing radionuclides are used in clinical trials as tumor-imaging agents or in positron emission tomography.
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Tài liệu tham khảo
Langer R., 1998, Nature,, 392, 5
Cattel L., 1999, A review. STP Pharma Sci,, 9, 307
Frankel A.E., 2000, Clin Cancer Res,, 6, 326
Vasey P.A., 1999, Clin Cancer Res,, 5, 83
Lundberg B., 1994, Anticancer Drug Des,, 9, 471
Bangham A.D., 1980, In: Liposomes in biological systems
Poste G., 1983, Biol Cell,, 47, 19
Federico M., 2001, In: Therapy perspectives,, 1
Cowens J.W., 1993, Cancer Res,, 53, 2796
Jain R.K., 1990, Cancer Res,, 50, 814S
Gabizon A.A., 1994, Hematol Oncol Clin North Am,, 8, 431
Senior J.H., 1987, Crit Rev Ther Drug Carrier Syst,, 3, 123
Chow D.D., 1989, J Pharmacol Exp Ther,, 248, 506
Michieli M., 1999, Haematologica,, 84, 1151
Forssen E.A., 1996, Cancer Res,, 56, 2066
Martin FJ., 1997, Oncology, 11, 11
Gabizon A., 1994, Cancer Res,, 54, 987
Northfelt D.W., 1997, Oncology,, 11, 21
Muggia F.M., 1997, Oncology,, 11, 38
Baselga J., 1998, Cancer Res,, 58, 2825
Gao X., 1995, Gene Ther,, 2, 710
Ogihara-Umeda I., 1996, J Nucl Med,, 37, 326
van Bree C., 1996, Cancer Res,, 56, 563