PolyAmp: A Novel Polymer Complexed Formulation of Amphotericin B

Ref ID: 19297

Author:

K. Les, T. Barata, J-w. Choi, V. Yardley, S. Brocchini, A. Godwin

Author address:

PolyTherics Ltd, London, United Kingdom; UCL Sch. of Pharmacy, London, United Kingdom; London Sch. of Hygiene & Tropical Med., London, United Kingdom.

Full conference title:

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy

Date: 10 September 2014

Abstract:

Background: Amphotericin B (AmB) is used to treat fungal infections and a neglected parasitic disease called visceral leishmaniasis (VL). Although AmB is very effective with little resistance reported, it has a narrow therapeutic window. Several AmB formulations are available with liposomal AmB (AmBisome® ) being the most efficacious against VL, with the best safety profile. However, requirement for cold chain supply in areas where VL is most prevalent can be cost prohibitive. AmB complexed with a polymer (PolyAmpâ„¢) has been developed as a cost effective alternative to AmBisome® . PolyAmpâ„¢ comprises AmB complexed to a low-cost, biodegradable polymer. This new formulation is heat stable and is expected to tolerate the high temperatures in countries where VL is most prevalent, allowing for distribution without cooling. Methods: PolyAmpâ„¢ was prepared as a freeze dried solid using a proprietary process where AmB was mixed with a polymer solution to enable complexation. The haemolytic activity of PolyAmpâ„¢ was determined in human red blood cells (RBCs) at 100 μg/mL of AmB and compared to Fungizone® at the same AmB concentration. The efficacy of PolyAmpâ„¢ was determined in a mouse model of VL (L. donovani HU3). PolyAmpâ„¢ was administered intravenously as three injections at 0.3, 1, 3 and 10 mg/kg doses per injection, based on AmB loading. AmBisome® was used as a control at the same dosing schedule. Results: PolyAmpâ„¢
showed similar physicochemical properties to AmBisome® .
PolyAmpâ„¢ did not haemolyse RBCs; less than 5% lysis
was observed after 24 h incubation. Fungizone® displayed
> 60% haemolysis under the same conditions. The low
haemolytic activity of PolyAmpâ„¢ translated into good in
vivo tolerability with no adverse effects observed in the
mice after a cumulative dose of 30 mg/kg of AmB. The
ED50 of PolyAmpâ„¢ was 0.32 mg/kg, comparable to that of
AmBisome® of 0.26 mg/kg. Conclusions: PolyAmpâ„¢ was
produced with similar physicochemical properties to
AmBisome® . PolyAmpâ„¢ was not haemolytic in vitro and
was well-tolerated in mice. The in vivo activity of
PolyAmpâ„¢ in a model of VL was similar to that of
AmBisome® . PolyAmpâ„¢ is therefore a promising candidate
for development as a new AmB formulation to treat VL.

Abstract Number: NULL

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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