Posaconazole-Loaded Leukocytes as a Novel Treatment Strategy Targeting Invasive Pulmonary Aspergillosis.

ABSTRACT:

Background

Impaired delivery of antifungals to hyphae within necrotic lesions is thought to contribute to therapeutic failure in invasive pulmonary aspergillosis (IPA). We hypothesized that transfusion of leukocytes loaded ex vivo with the lipophilic antifungal posaconazole could improve delivery of antifungals to the sites of established infection and improve outcome in experimental IPA.

Methods

The HL-60 leukemia cell line was differentiated to a neutrophil-like phenotype (differentiated HL-60 [dHL-60] cells) and then exposed to a range of posaconazole concentrations. The functional capacity and antifungal activity of these cells were assessed in vitro and in a mouse model of IPA.

Results

Posaconazole levels in dHL-60 cells were 265-fold greater than the exposure co

SUBMITTER: Baistrocchi SR 

PROVIDER: S-EPMC5853238 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature