Tailoring liposomes for cancer drug delivery: from the bench to the clinic.
Sterically stabilized liposomes with prolonged circulation times, also referred to as 'Stealth', accumulate in significant amounts in transplanted tumors. Morphological studies carried out with colloidal-gold labeled liposomes show that liposomes can extravasate and localize in the extracellular space of tumors implanted in mice, a phenomenon which is apparently related to the increased permeability of the tumor microvasculature. When these long-circulating liposomes are loaded with doxorubicin, the drug circulates in liposome-associated form and is cleared very slowly from plasma. The drug levels in the heart muscle are drastically diminished, while those in the tumor tissue are significantly raised by liposome encapsulation. Doxorubicin in Stealth liposomes was also shown to have reduced toxicity and greater therapeutic efficacy than free doxorubicin in a mouse tumor model. We conclude that properly formulated liposomes with long residence times in circulation offer a promising tool to improve the therapeutic index of cancer chemotherapeutic agents.
Gabizon
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Sharett Institute of Oncology, Hadassah University Hospital, Jerusalem, Israel.
D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D008081:Liposomes; D051379:Mice
D008081:Liposomes; D004317:Doxorubicin