The burden of drug resistance emerges in the wake of chronic and repeated antibiotic
use. This underpins the importance of discovering alternatives to current antibiotic
regimens. In chronic rhinosinusitis (CRS), topical therapy such as nasal douches and
steroid sprays is the mainstay of treatment. However, bacterial sinusitis such as
those with Staphylococcus aureus biofilm infection point to more recalcitrant CRS subtypes, focusing research efforts
into topical antimicrobial therapies. In the sinuses, both local mucosal and systemic
effects must be considered in designing any new topical medication. Nitric oxide (NO),
an endogenous antimicrobial agent, is found at extremely low levels in CRS sinuses
and high levels in healthy sinuses. As a novel treatment modality, we have designed
a liposomal formulation of an NO donor (LFNO) using isosorbide mononitrate, as a topical
sinus wash in a sheep model of S. aureus biofilm rhinosinusitis. Heart rate (HR), blood pressure, mean arterial pressure (MAP),
and histologic and ciliary analyses were assessed in the safety component. Efficacy
was assessed by quantifying biofilm biomass post-treatment. LFNO-treated sheep had
lesser inflammation (P = 0.02), and comparable ciliary preservation (P = 0.86) than the control group. A transient increase in HR and decrease in MAP were
observed in the LFNO group (P < 0.05), but this was not accompanied by observable side effects. LFNO sheep had
significantly lower biofilm biomass vs controls (P = 0.044). Our findings demonstrate the localized and systemic safety of LFNO in an
animal model despite using high NO concentrations, thus warranting further investigation
for its possible therapeutic role in CRS.
Abbreviations:
ATCC (American type culture collection), BP (blood pressure), bpm (beats per minute), CRS (chronic rhinosinusitis), FISH (fluorescence in situ hybridization), HR (heart rate), ISMN (isosorbide mononitrate), LB (blank liposomes), LFNO (liposomal-formulated nitric oxide), MAP (mean arterial pressure), MBEC (minimum biofilm eradication device), MFU (McFarland unit), MLV (multilamellar vesicles), NO (nitric oxide), PBS (phosphate buffered solution), PdI (polydispersity index), S. aureus (Staphylococcus aureus), SEM (scanning electron microscopy), ULV (unilamellar vesicles)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: June 23, 2015
Accepted:
June 16,
2015
Received in revised form:
June 14,
2015
Received:
April 8,
2015
Identification
Copyright
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
