Verlängerte biologische Halbwertszeit der sulfatierten Mukopolysaccharide bei Alloxandiabetes als Ursache der diabetischen Mesenchymstoffwechselstörung

Peer Reviewe

Pulsating aerosols for drug delivery to the sinuses in healthy volunteers.

OBJECTIVE: Approximately 10 to 15 percent of the European and U.S. population have chronic rhinosinusitis, but effective treatment remains a challenge. There has been limited success using topical drug delivery to the nose and the paranasal cavities/sinuses, in part because most nasally administered aerosol drug formulations are efficiently filtered at the nasal valve and fail to reach the osteomeatal area and sinuses. STUDY DESIGN: Feasibility study. SETTING: Nuclear medicine department. SUBJECTS AND METHODS: Pulsating airflows were applied to the nasal cavity and sinus ventilation was studied in five healthy human volunteers using dynamic (81m)Kr-gas gamma camera imaging. Furthermore, deposition and retention of (99m)Tc-DTPA radiolabeled aerosols delivered by nasal pump sprays or by pulsating aerosols was assessed in each volunteer over a 24-hour period. RESULTS: Only the pulsating airflow demonstrated efficient (81m)Kr-gas ventilation of the paranasal sinuses. No drug was deposited into the sinuses using nasal pump sprays, but up to 6.5 percent of the nasally administered drug was deposited into the sinuses using pulsating airflow. Clearance kinetics of the drug was reduced after pulsating aerosol delivery compared to nasal pump sprays. Residence time of the drug at the site of deposition was up to three-fold longer with pulsating aerosol delivery than with nasal pump sprays. CONCLUSION: Our data support the hypothesis that topical drug delivery in relevant quantities to the nose and osteomeatal areas, including the paranasal sinuses, is possible using pulsating airflows. Furthermore, the frequency of drug applications may be reduced due to a delayed clearance and longer residence time

Ventilation and aerosolized drug delivery to the paranasal sinuses using pulsating airflow: A preliminary study.

Although there is a high incidence of nasal disorders including chronic sinusitis, there is limited success in the topical drug delivery to the nose and the paranasal sinuses. This is caused by the nose being an efficient filter for inhaled aerosol particles and the paranasal sinuses being virtually non-ventilated. Method: The objective of this study was to visualize the efficiency of sinus ventilation in healthy volunteers using dynamic 81mKr-gas imaging in combination with pulsating airflows. Furthermore, the deposition and retention of 99mTc-DTPA aerosol particles was assessed. Results: The ventilation of the maxillary and frontal sinuses could be visualized by gamma camera imaging during pulsating airflow. In addition, using pulsating airflow, between 3% and 5% of nasally deposited aerosols penetrated into the paranasal sinuses while during application without pulsation aerosol deposition was below 1%. Furthermore pulsation increased aerosol deposition in the nasal airways by a factor of three. Conclusions: The study demonstrates the high efficiency of a pulsating airflow in paranasal sinus ventilation and aerosolized drug delivery. This proves that topical drug delivery to the paranasal sinuses in relevant quantities is possible and indicates further clinical studies are necesarry