Background:
To address multidrug resistance we developed engineered cationic antimicrobial peptides
(eCAPs). Lead eCAP WLBU2 displays potent activity against drug-resistant bacteria and effectively treats lethal bacterial
infections in mice reducing bacterial loads to undetectable levels in diverse organs.
Background:
To address multidrug resistance we developed engineered cationic antimicrobial peptides
(eCAPs). Lead eCAP WLBU2 displays potent activity against drug-resistant bacteria and effectively treats lethal bacterial
infections in mice reducing bacterial loads to undetectable levels in diverse organs.
Objective:
To support development of WLBU2, we conducted a mass balance study.
Methods:
CD1 mice were administered 10, 15, 20 and 30 mg/kg QDx5 WLBU2 or a single dose of [14C]-WLBU2 at 15
mg/kg IV. Tolerability, tissue distribution and excretion were evaluated with liquid scintillation and HPLCradiochromatography.
Results:
The maximum tolerated dose of WLBU2 is 20 mg/kg IV. We could account for greater than >96% of the
radioactivity distributed within mouse tissues at 5 and 15 min. By 24 h, only ~40-50% of radioactivity remained in the
mice. The greatest % of the dose was present in liver, accounting for ~35% of radioactivity at 5 and 15 min, and ~ 8% of
radioactivity remained at 24 h. High radioactivity was also present in kidneys, plasma, red blood cells and lungs, while
less than 0.2% of radioactivity was present in brain, fat, or skeletal muscle. Urinary and fecal excretion accounted for 12.5
and 2.2% of radioactivity at 24 h.
Conclusion:
WLBU2 distributes widely to mouse tissues and is rapidly cleared with a terminal radioactivity half-life of
22 h, a clearance of 27.4 mL/h/kg, and a distribution volume of 0.94 L/kg. At 2-100 µg-eq/g, the concentrations of 14CWLBU2 appear high enough in the tissues to account for inhibition of microbial growth.
Nanoparticles Enable Efficient Delivery of Antimicrobial Peptides for the Treatment of Deep Infections
