In Vivo Biodistribution of Inhaled Colistin-Endolysin Combination
Pengfei Zhang1, Ping Zeng1 & Sharon S. Y. Leung1
1 School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR
Summary
The rapid emergence of multidrug-resistant (MDR) bacteria, particularly the gram-negative (G-ve) ones, has significantly increased the medical challenges in managing their associated pneumonia. Combination therapy of colistin with bacteriophage-derived endolysins (lysins) has recently attracted significant attention to combat infections caused by MDR G-ve bacteria. To maximize the synergy of the combination treatment, it is essential to maintain the two agents at an optimal mixing ratio at the infection sites. In the present study, we investigated the lung retention time of colistin and LysAB2 lysin in healthy BALB/c mice via intratracheal (IT) aerosolization and intravenous (IV) injection. Anaesthetized mice were dosed with fluorescence-labelled colistin (with sulfo-cy5) and LysAB2 (with sulfo-cy7). At designated time points (1, 2, 4, 8, and 24 h), the distribution of both agents was monitored through fluorescence measurement with an in-vivo animal imaging system (IVIS). Our results showed colistin and LysAB2 shared similar biodistribution profiles regardless of the administration routes. Compared with IV injection, colistin and LysAB2 delivered via IT aerosolization had apparently higher and longer lung exposure. The promising data suggest that the optimal mixing ratio of the two agents from in-vitro setting can be applied for in-vivo experiments with minimum adjustment.