University of Texas – Austin
Carvalho, Thiago Cardoso.
Development of an inhalational formulation of Coenzyme Q₁₀ to treat lung malignancies.
Degree: PhD, Pharmacy, 2011, University of Texas – Austin
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.
Advisors/Committee Members: McConville, Jason Thomas (advisor).
Subjects/Keywords: Formulation; Inhalation; Lung cancer; Chemotherapy; Coenzyme Q₁₀; Ubiquinone; Ubidecarenone; Nebulization; Colloidal dispersions; Phospholipids; High pressure homogenization; Microfluidization; Rheology; Surface tension; Particle size; Zeta potential; Maximum pull on a disk; Aerodynamic deposition
to Zotero / EndNote / Reference
APA (6th Edition):
Carvalho, T. C. (2011). Development of an inhalational formulation of Coenzyme Q₁₀ to treat lung malignancies. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/21556
Chicago Manual of Style (16th Edition):
Carvalho, Thiago Cardoso. “Development of an inhalational formulation of Coenzyme Q₁₀ to treat lung malignancies.” 2011. Doctoral Dissertation, University of Texas – Austin. Accessed September 30, 2020.
MLA Handbook (7th Edition):
Carvalho, Thiago Cardoso. “Development of an inhalational formulation of Coenzyme Q₁₀ to treat lung malignancies.” 2011. Web. 30 Sep 2020.
Carvalho TC. Development of an inhalational formulation of Coenzyme Q₁₀ to treat lung malignancies. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2011. [cited 2020 Sep 30].
Available from: http://hdl.handle.net/2152/21556.
Council of Science Editors:
Carvalho TC. Development of an inhalational formulation of Coenzyme Q₁₀ to treat lung malignancies. [Doctoral Dissertation]. University of Texas – Austin; 2011. Available from: http://hdl.handle.net/2152/21556