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Because of the reduced toxicity associated with liposomal amphotericin B preparations, different amphotericin B liposome products have been made. In the present study, we compared the amphotericin B liposomal formulations, AmBisome(®) (AmBi) and Lambin(®) (Lbn), in uninfected and Aspergillus fumigatus infected mice, using several in vitro and in vivo toxicity and efficacy assays. The results showed that the formulations were significantly different, with Lbn 1.6-fold larger than AmBi. Lbn was also more toxic than AmBi based on the RBC potassium release assay and intravenous dosing in uninfected mice given a single 50 mg/kg dose (80% mortality for Lbn vs. 0% for AmBi). Renal tubular changes after intravenous daily dosing for 14 days were seen in uninfected mice given 5 mg/kg Lbn but not with AmBi. Survival following A. fumigatus challenge was 30% for 10 mg/kg Lbn and 60% for 10 mg/kg AmBi. When the BAL and lungs were collected 24 h after the second treatment, AmBi at 10 or 15 mg/kg or 15 mg/kg Lbn lowered the BAL fungal burden significantly vs. the controls (P ≤ 0.05), while there was no difference in lung fungal burden amongst the groups. In contrast, lung histopathology at this same early timepoint showed that AmBi was associated with markedly fewer fungal elements and less lung tissue damage than Lbn. In conclusion, given the differences in size, toxicity, and efficacy, AmBi and Lbn were not physically or functionally comparable, and these differences underscore the need for adequate testing when comparing amphotericin B liposome formulations.

In the early 1980s, Vestar Inc., a company founded on the basis of science developed by the California Institute of Technology and the City of Hope, brought into development an imaging agent based on liposome encapsulated (111)In(3+). This agent, named Vescan, together with the gamma ray perturbed angular correlation spectroscopy technique to examine liposome integrity, was envisioned as a broadly applicable in vivo tumor diagnostic agent. While not ultimately commercialized, the agent was used to successfully image a variety of tumors, and was evaluated in late-stage clinical trials. Lessons learned from the formulation and process development of this product, and the wealth of non-clinical and clinical results, revealed valuable information about the properties of stable, RES avoiding conventional liposomes. This technology ultimately would lead (at NeXstar Pharmaceuticals and, later, at Gilead Sciences) to the technology that created commercialized liposomal products such as AmBisome and DaunoXome as well as other development stage product candidates.

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