Journal ArticleDOI
Treatment and Prophylaxis of Disseminated Infection Due to Candida albicans in Mice with Liposome-Encapsulated Amphotericin B
Gabriel Lopez-Berestein,Reeta Mehta,R. L. Hopfer,K. Mills,L. P. Kasi,Kapil Mehta,Victor Fainstein,Mario A. Luna,Evan M. Hersh,R. L. Juliano +9 more
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TLDR
The encapsulated drug was as effective as the free drug when used in similar concentrations, while the animals treated with higher concentrations of liposomal amphotericin B had a longer survival time and an improved therapeutic index resulted by encapsulating amph esotericin B in liposomes.Abstract:
The toxicology of liposome-encapsulated amphotericin B in mice and its efficacy in the treatment and prophylaxis of systemic candidiasis in these animals were studied. The toxicology studies indicated that the maximal tolerated dose of free amphotericin B was 0.8 mg/kg of body weight and the 50% lethal dose (LD50) was reached at 1.2 mg/kg, while neither the maximal tolerated dose nor the LD50 for the liposomal amphotericin B was reached at a dose of 12 mg/kg. No abnormalities in blood chemistry or histology were observed in the animals injected with encapsulated amphotericin B, while the administration of free amphotericin B was associated with nephrocalcinosis and renal parenchymal edema. The encapsulated drug was as effective as the free drug when used in similar concentrations, while the animals treated with higher concentrations of liposomal amphotericin B (4 mg/kg) had a longer survival time. Thus, an improved therapeutic index resulted by encapsulating amphotericin B in liposomes.read more
Citations
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Journal ArticleDOI
Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors.
TL;DR: By selective changes in lipid composition, up to a 60-fold increase in the fraction of recovered dose present in blood 24 hr after i.v. injection is achieved, which has considerable therapeutic potential in cancer for increasing the concentration of cytotoxic agents in tumors while minimizing the likelihood of toxicity to the reticuloendothelial system.
Journal ArticleDOI
Amphotericin B: 30 Years of Clinical Experience
TL;DR: The clinical uses of amphotericin B are discussed, including its application in AIDS-related fungal infections, in neutropenic cancer patients who are persistently febrile, and in infections of the central nervous system, lung, peritoneum, genitourinary system, eye, and skin.
Journal ArticleDOI
Clinical Translation of Nanomedicine.
TL;DR: The typical clinical translation path for a new drug starts with investigators generating robust preclinical data to demonstrate the safety and efficacy of the new drug to enable an investigational new drug (IND) application with the Food and Drug Administration (FDA).
Journal ArticleDOI
Liposomal Amphotericin B for the Treatment of Systemic Fungal Infections in Patients with Cancer: A Preliminary Study
Gabriel Lopez-Berestein,Victor Fainstein,Roy L. Hopfer,Kapil Mehta,Margaret P. Sullivan,Michael J. Keating,Michael G. Rosenblum,Reeta Mehta,Mario A. Luna,Evan M. Hersh,James M. Reuben,Rudolph L. Juliano,Gerald P. Bodey +12 more
TL;DR: Twelve patients with hematologic malignancies complicated by fungal infections were treated with liposomal amphotericin B (L-AmpB); nine patients were granulocytopenic; the three additional patients with normal granulocyte counts were immunosuppressed.
Book
Liposomes in Drug Delivery
TL;DR: A large number of trials in patients with cancer or infections suggest that certain liposomal drug formulations are likely to prove clinically useful, and liposome-entrapped drugs and vaccines exhibit superior pharmacological properties to those observed with conventional formulations.
References
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