Ventilation and aerosolized drug delivery to the paranasal sinuses using pulsating airflow

by Möller et al. 2009

This paper discusses, sinusitis and rhinosinusitis. The was to develop a better treatment method for these infections. Sinusitis is a commonly diagnosed illnesses in European population, it is also estimated that over 10 -15% of the European population suffers from rhinosinusitis. Sinusitis and chronic rhinosinusitis a result of inflamed nasal lining due to bacterial, fungal and allergic infections. Inflammation of nasal mucus lining will result in an increased mucus secretion, loss of cilia, obstructed air pathway and blockage of nasal drainage. This will lead to loss of mucus drainage and in turn sinusitis while chronic rhinosinusitis is observed in an environment with reduced ventilation.

In vivo and in vitro studies have indicated that paranasal sinus could be reached through nebulized drugs but it was noted that it only had a low efficiency, therefor the main treatment method for chronic sinusitis and rhinosinusitis still remains as surgery. It is important to find a better treatment and transportation method of drugs for treatment of these infections.
This study aims to analyse the ventilation efficiency of the sinus of three healthy volunteers, using dynamic 81mKr-gas imaging along with pulsating airflows. The researchers also study and investigate the deposition efficiency by radiolabeling the aerosols with DTPA(diethylenetriaminepentaacetic acid) and retention of 99mTc-DTPA aerosol particles after a period of 24 hours was assessed.

Three healthy male volunteers (non-smokers) with a mean age of 46+/- 12 were recruited to participate in this study. All three volunteer’s has normal lung functions and had no history of allergic diseases. Nasal anatomies of the three subjects were investigated with use of MRT imaging and fibre optic rhinoscopy.
Pulsating aerosol delivery system.

PARI SINUS system with 45Hz frequency with amplitude of 24mbar was used to generate a pulsating aerosol generating system based on PARI BOY N aerosol drug delivery device. The rate of mass output was at 0.2ml/min, There was no significance difference between pulsating aerosol output and non-pulsating aerosol output was noted.
Kr-gas ventilation studies. Contineous ventilation of Kr-gas through nasal airway was given in front of a single head gamma camera with the use of PARI SINUS system the air supply has 82mKr- gas generator output channel. Kr-gas ventilation imaged was taken with and without pulsation for comparison.

The aerosol was produced using a solution composed of 99mTc- DTPA (diethylenetriaminepentaacetic acid) with nanocolloid of 500 Dalton in size. DTPA aerosols constructed were used for ventilation imaging and measurement of alveolar transmembrane permeability. Passive diffusion results in clearing out of 99mTc-DTPA within 90 minfrom the lungs into circulation. Nebulizer was filled with DTPA solution containing about 600 MBq of 99mTc-activity. Total nasal deposition rate was assessed by measuring the output rate of the nebulizer all particles on PALL BB50 filter before the aerosol delivery. Post DTPA delivery was measured during 24hours by investigating the nasal deposition, retention and clearance along with low energy collimator. Images of anterior and lateral gamma camera were coded just after inhalation, and after 1.5, 3, 6 and 24 hours post inhalation respectively. DTPA Translocate to blood after 24 hours was assessed by urine analysis. Statistical analyses of group difference of with or without pulsation were performed and calculated by two-sided t-Test with a significance level of p < 0.05.

There is only little Kr- gas pentration to the paranasal sinus is seen, this is clearer since sinus do not appear on this image.

Images suggest negligible Kr- gas activity in the maxillary sinuses. Kr-gas penetration was seen in the nasal airway when administrated without pulsation while with pulsating the gas penetration was seen to front sinus resulting in activity above the nasal airways and Kr-gas penetration to maxillary sinuses shows activity to central nasal activity region and below. The images demonstrate Kr-gas activity in central nasal cavity and the frontal and maxillary sinus in all three volunteers. There were no difference in activity was visualized in central nasal cavity due to pulsating air flow after normalization for the activity of the nebulizer, But a 5 fold incur of activity in four sinus with pulsation air flow was observed.

Aerosol deposition in the nasal airways and in the nasal sinuses
Aerosol deposition was not recovered in the first image obtained after immediate aerosol deliver confirming tight closure of the soft plate during aerosol delivery. Three subject showed total aerosol deposition (% of nebulized dose) of 25 ± 16% without pulsation and 58 ± 17% with pulsation (p < 0.01) in the nasal cavitiy. Pentration to the sinuse was ovserved at 4.2 ± 0.3% with plkkusation with 1% was seen for without pulsation.

DTPA clearance from the nasal cavity
Aerosols delivered with and without pulsation deposited were cleared with half time of 1 hours according for nearly 30% of the aerosols. The remained were cleared with half time 6.9 and 7.9 hours for both with and without pulsation aerosol delivery. Retention of aerosol without and with pulsating delivery in nasal cavity after 24 hours were observed at 5.4 ± 1.8% and 8.6 ± 1.3% respectively while a( p < 0.01) DTPA was excreted into the urine within 24 hours.

Ventilation of maxillary and frontal sinuses was observed by gamma camera was observed with pulsating air flow with an deposited aerosol penetration of 3% to 5% into the paranasal sinus with pulsating delivery system where as only 1% was seen when administrated via non pulsation. There for pulsation has increased aerosol deposit in the nasal airway by factor of three.
The data suggests that paranasal sinus ventilation air flow and aerosolized drug delivery showed high efficiency when given via pulsating air flow. The data therefore suggest that topical drug delivery to paranasal sinus in relevant quantities could be a possible future treatment instead of surgery with further investigations. The data presented in this study only uses three volunteer’s which is not a sufficient number of test subjects there for further investigation should be recommended. The three subjects were healthy with clear air pathways; therefore for treatment of chronic rhinosinusitis the data may not be applicable.

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One response

  1. Prof Waqar Ahmed | Reply

    Good summary. Please add full reference to the paper that is being summarised

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