Why the study?
Does adriamycin entrapped in cholesterol sulfate-containing liposomes improve pharmacokinetics and antineoplastic activity compared to free adriamycin in mice?
Does adriamycin entrapped in cholesterol sulfate-containing liposomes improve pharmacokinetics and antineoplastic activity compared to free adriamycin in mice?
Entrapment of adriamycin in cholesterol sulfate-containing liposomes improves its pharmacokinetic profile, reduces cardiac accumulation, and enhances antineoplastic activity in a murine leukemia model.
Should not yet change adriamycin use in patients; leaves open translation of liposomal formulations to clinical oncology trials.
Pharmacokinetics and antineoplastic effect of adriamycin (ADM) entrapped in multilamellar vesicles of liposomes composed of egg phosphatidylcholine (PC), cholesterol (Chol), and cholesterol sulfate (CholSO4) in a molar ratio of 6:3:1 were studied. Upon its intravenous injection, the blood level of ADM remained higher for 24h than that of ADM entrapped in liposomes composed of PC, Chol, and sulfatide (CSE) in a molar ratio of 5:4:1 and than that of free ADM. Entrapment of ADM in liposomes containing either CholSO4 or CSE reduced the concentration of ADM in the heart and kidney compared with free ADM. In the liver, however, the level of ADM, when the drug entrapped in CholSO4-containing liposomes was injected, was similar to that of ADM injected in free form, while the drug markedly accumulated in this organ, when ADM was entrapped in CSE-containing liposomes. By using P388 leukemia of mice, we demonstrated that ADM entrapped in CholSO4-containing liposomes has higher antineoplastic activity than free ADM.
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Noda et al. (1991) studied this question.
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