CSI-Sydney: New technologies to treat chronic sinus infection APP1076217

Project Member(s): Whitchurch, C.

Funding or Partner Organisation: National Health & Medical Research Council (National Health Medical Research Council)

Start year: 2014

Summary: There is no current marketed nasal aerosol medicine for the treatment of chronic sinus infection (CSI), or an `efficient device¿ capable of specific targeting. The only current device is the PARI SINUS, which only deliver 6.5% of the dose to the target regions, has lengthy treatment times (~4min) and a high potential for lung deposition. We will develop and test a novel clinical prototype device (based on the sono-capillary effect). The device will be optimised for rapid drug delivery (3s) target the sinus region through a pulsed airflow and will avoid lung deposition through modification of particle size. Simultaneously, we will develop a formulation, capable of removing mucus, dispersing biofilms and killing bacteria that can be incorporated into the device. We will develop a series of nasal casts from CT data that can be used to study and optimise sinus targeting (current commercially available sinus models are impractical and do not contain Frontal or Maxillary sinus regions). The influence of device power and pulsation frequency will be investigated using the casts and provide the basis for settings used in a 99mTc-DTPA radiolabeled scintigraphic study. Simultaneously, we will evaluate the effect of a broad-spectrum antibiotic (ciprofloxacin), mucolytic (Xylitol) and bio-dispersant (cis-2- decenoic acid) on a series of epithelia cell cultures and bio-film models (including a co-culture). We study the effectiveness, toxicity and synergistic effect using these cell models and undertake pharmacokinetic studies using a small animal model. At the conclusion of this Development Grant will be in a position to register the nasal drug delivery device for use with a wide-range of currently available drugs and have a combination therapy which targets CSI ready for first-in-human trials.

Keywords: nasal delivery, aerosol therapy, biofilm, bacterial infection, imaging

FOR Codes: Respiratory System and Diseases (incl. Asthma), Pharmacology and Pharmaceutical Sciences not elsewhere classified, Clinical health

Acknowledgement of Country

UTS acknowledges the Gadigal people of the Eora Nation, the Boorooberongal people of the Dharug Nation, the Bidiagal people and the Gamaygal people, upon whose ancestral lands our university stands. We would also like to pay respect to the Elders both past and present, acknowledging them as the traditional custodians of knowledge for these lands.