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Abstract:
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Cancer is the second leading cause of death in the United States and its onset is highly incident in the lungs , with very low long -term survival rates . Chemotherapy plays a significant role for lung cancer treatment , and pulmonary delivery may be a potential route for anticancer drug delivery to treat lung tumors . Coenzyme Q₁₀ (CoQ₁₀ ) is a poorly -water soluble compound that is being investigated for the treatment of carcinomas . In this work , we hypothesize that formulations of CoQ10 may be developed for pulmonary delivery with a satisfactory pharmacokinetic profile that will have the potential to improve a pharmacodynamic response when treating lung malignancies . The formulation design was to use a vibrating -mesh nebulizer to aerosolize aqueous dispersions of CoQ₁₀ stabilized by phospholipids physiologically found in the lungs . In the first study , a method was developed to measure the surface tension of liquids , a physicochemical property that has been shown to influence the aerosol output characteristics from vibrating -mesh nebulizers . Subsequently , this method was used , together with analysis of particle size distribution , zeta potential , and rheology , to further evaluate the factors influencing the capability of this nebulizer system to continuously and steadily aerosolize formulations of CoQ₁₀ prepared with high pressure homogenization . The aerosolization profile (nebulization performance and in vitro drug deposition of nebulized droplets ) of formulations prepared with soybean lecithin , dimyristoylphosphatidylcholine (DMPC ) , dipalmitoylphosphatidylcholine (DPPC ) and distearoylphosphatidylcholine (DSPC ) were evaluated . The rheological behavior of these dispersions was found to be the factor that may be indicative of the aerosolization output profile . Finally , the pulmonary deposition and systemic distribution of CoQ₁₀ prepared as DMPC , DPPC , and DSPC dispersions were investigated in vivo in mice . It was found that high drug amounts were deposited and retained in the mouse lungs for at least 48 hours post nebulization . Systemic distribution was not observed and deposition in the nasal cavity occurred at a lower scale than in the lungs . This body of work provides evidence that CoQ₁₀ may be successfully formulated as dispersions to be aerosolized using vibrating -mesh nebulizers and achieve high drug deposition in the lungs during inhalation . |