NanoDisk-Amphotericin B is Superior to Liposomal Amphotericin B in a Murine Model of Disseminated Aspergillosis

Ref ID: 18690

Author:

B. L. Burgess, MS – Scientist1,2, Y. He, BS – RA 2, B. Luo, MS – Sr. Scientist 1, R. O. Ryan, PhD – Sr Scientist 1,2, S. F. Carroll, PhD – Director, Discovery and Development 1, T. M. Forte, PhD – Staff Scientist 1,2, M. N. Oda, PhD – Sr Scientist 1,

Author address:

1Lypro Biosciences, Berkeley, CA, 2Children’s Hosp. Oakland, Oakland, CA.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: We have developed a novel formulation of Amphotericin B (NanoDisk-AMB) for treatment of invasive pulmonary aspergillosis (IPA). Despite existing first line therapies for IPA, including AMB, mortality rates remain greater than 50%. NanoDisk is a self-assembling bioparticle, 20-30 nm in diameter, designed to facilitate delivery of hydrophobic therapeutics. We have demonstrated that NanoDisk-AMB (ND-AMB) has a favorable in vivo safety profile, yet remains highly potent versus Aspergillus fumigatus, with an MIC of 0.5 μg/mL, 6-fold lower than AmBisome (liposomal AMB). Methods: To more accurately model invasive disease, standard (early) and late-stage (delayed) models of A.fumigatus were used to confirm the in vivo efficacy of ND-AMB. Immuno-normal mice were challenged i.v. with A. fumigatus (Af293). Therapy, initiated 24 h or 48 h post-infection, included ND-AMB (n = 24-26) or AmBisome (n = 12-13) administered i.v. q1d for 5 days. A dose of 0.75 mg/kg/day AMB was employed to explore differences between therapies. Kidneys were harvested 3 days after the final treatment and fungal load was assayed by qPCR specific for fungal DNA. Results: Mice treated with ND-AMB had better survival, improved body weights and reduced fungal burden. Conclusions: ND-AMB elicits a rapid therapeutic effect and is superior to AmBisome for the treatment of systemic A. fumigatus in our model of late-stage infection. This finding suggests that ND-AMB will improve therapeutic outcomes for patients with IPA.

Abstract Number: F-2015b

Conference Poster: y

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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