Establishing the optimal nebulization system for paclitaxel, docetaxel, cisplatin, carboplatin and gemcitabine: Back to drawing the residual cup

Abstract

Chemotherapy drugs have still the major disadvantage of non-specific cytotoxic effects. Although, new drugs targeting the genome of the tumor are already in the market, doublet chemotherapy regimens still remain the cornerstone of lung cancer treatment. Novel modalities of administration are under investigation such as; aerosol, intratumoral and intravascular. In the present study five chemotherapy drugs; paclitaxel, docetaxel, gemcitabine, carboplatin and cisplatin were nebulized with three different jet nebulizers (Maxineb(®), Sunmist(®), Invacare(®)) and six different residual cups at different concentrations. The purpose of the study was to identify the "ideal" combination of nebulizer-residual cup design-drug-drug loading for a future concept of aerosol chemotherapy in lung cancer patients. The Mastersizer(®) 2000 was used to evaluate the aerosol droplet mass median aerodynamic diameter. The drug, nebulizer and residual cup design greatly influences the producing droplet size (p<0.005, in each case). However; the design of the residual cup is the most important factor affecting the produced droplet size (F=834.6, p<0.001). The drug loading plays a vital role in the production of the desired droplet size (F=10.42, p<0.001). The smallest droplet size was produced at 8 ml loading (1.26 μm), while it remained the same at 2, 4 and 6 mls of drug loading. The ideal nebulizer would be Maxineb(®), with a large residual cup (10 ml maximum loading capacity) and 8 mls loading and the drug with efficient pulmonary deposition would be docetaxel.