Lung deposition of aerosolized anticancer drugs with a novel inhalation system: AKITA

Abstract

12037 Background: Inhalation of anticancer drugs might be a helpful route of delivery in cancer therapy, particularly for lung tumors and metastasis in the lungs. In this experimental setup 12 different drugs (including antineoplastic drugs and immunotherapeutics) were nebulized with two different jet nebulizer systems. Aerosol particle size (MMD) and mass output were characterized. Methods: MMD was measured using a laser diffraction system (Sympatec, Clausthal-Zellerfeld, Germany). Mass output measurements were performed after CEN Standard using a Flow/volume simulator with radiolabelled (99m Tc) solution/suspension. The amount of radioactivity on the filters was detected with a scintillation counter. For aerosolization two nebulizer systems were used: Pari LC Plus with Pari compressor (PARI) and Pari LC Star with AKITA compressor (AKITA). To determine lung deposition a lung deposition model (International Commission of Radiological Protection, ICRP66, 1994) was used, taking into account: mass output, particle size and breathing pattern of patients. The AKITA guides the patient with a positive pressure through the inhalation maneuver, it is breath activated and delivers the medication only during inspiration. The PARI nebulizes continuously and the patient inhales with different individual breathing pattern. Results: MMD with PARI was found to be 4.2 ± 0.4 μm compared to 3.40 ± 0.3 μm for AKITA. After filling 2.5 ml into the nebulizers we found 1.4 ml residual volume with PARI and 1.0 ml for AKITA. The output rate was 0.15 ± 0.02 ml/min for PARI and 0.29 ± 0.03 ml/min for AKITA. Lung deposition relative to the emitted dose was determined to be 28 ± 10% for PARI and 85 ± 4% for AKITA. This is because the AKITA nebulizes only during inspiration and guides the patient through the inhalation maneuver, where as the PARI is running continuously and patients inhale with different breathing pattern. The result is that from 2.5 ml filled into the nebulizer, on average 0.3 ml will be deposited in the lungs with the PARI and 1.3 ml with the AKITA. To deposit 1 ml in the lungs with AKITA it will take 7 min, with PARI about 24 min. Conclusions: By use of modern inhalation devices with controlled inhalation lung deposition for cancer therapy can be optimized. [Table: see text]