Liposomal anticancer therapy: pharmacokinetic and clinical aspects.
Liposomes, which are vesicles composed of a phospholipid bilayer surrounding an aqueous milieu, represent a new strategy for anticancer drug delivery. Extravasation and accumulation of liposomal drugs within neoplastic tissues are possible because of the leaky vasculature and scarce lymphatic vessels of tumours (the enhanced permeability and retention effect). Furthermore, liposomal chemotherapeutic agents display distinctive pharmacokinetic characteristics, because they possess longer elimination half-lives, reduced clearance and smaller volume of distribution with respect to corresponding free drugs. Taken together, these features lead to highest levels of cytotoxic agents in tumours, as demonstrated in preclinical models and clinical trials, whereas healthy tissues are spared from toxicity. In fact, liposomal drugs (i.e., doxorubicin), alone or in combination with other cytotoxic agents, lead to improved clinical effectiveness and ameliorated toxicity profile with respect to corresponding free drugs when they are used for the treatment of metastatic breast and ovarian cancers, and Kaposi's sarcoma.
Di Paolo
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Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy. a.dipaolo@ao-pisa.toscana.it
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004337:Drug Carriers / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008081:Liposomes / Q000494:pharmacology* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D012680:Sensitivity and Specificity
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin