Formulation and cytotoxicity of doxorubicin nanoparticles carried by dry powder aerosol particles - Spray Freeze-Drying

Formulation and cytotoxicity of doxorubicin nanoparticles carried by dry powder aerosol particles
Received 12 January 2006; revised 27 March 2006; accepted 28 March 2006. Available online 18 April 2006.
Shirzad Azarmia, b, c, Xia Taoa, c, Hua Chena, Zhaolin Wangd, Warren H. Finlayd, Raimar L?benberga, , , and Wilson H. Roac
International Journal of Pharmaceutics
Volume 319, Issues 1-2 , 17 August 2006
ScienceDirect
Copyright ? 2006 Elsevier B.V. All rights reserved.
aFaculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alta., Canada T6G 2N8
bResearch Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
cDepartment of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, Alta., Canada T6G 1Z2
dDepartment of Mechanical Engineering, University of Alberta, Edmonton, Alta., Canada T6G 2G8
Abstract
Regional drug delivery via dry powder inhalers offers many advantages in the management of pharmaceutical compounds for the prevention and treatment of respiratory diseases. In the present study, doxorubicin (DOX)-loaded nanoparticles were incorporated as colloidal drug delivery system into inhalable carrier particles using a spray-freeze-drying technique. The cytotoxic effects of free DOX, carrier particles containing blank nanoparticles or DOX-loaded nanoparticles on H460 and A549 lung cancer cells were assessed using a colorimetric XTT cell viability assay. The mean geometric carrier particle size of 10 ? 4 ?m was determined using confocal laser scanning microscopy. DOX-loaded nanoparticles had a particle size of 173 ? 43 nm after re-dissolving of the carrier particles. Compared to H460 cells, A549 cells showed less sensitivity to the treatment with free DOX. The DOX-nanoparticles showed in both cell lines a higher cytotoxicity at the highest tested concentration compared to the blank nanoparticles and the free DOX. The cell uptake of free DOX and DOX delivered by nanoparticles was confirmed using confocal laser scanning microscopy. This study supports the approach of lung cancer treatment using nanoparticles in dry powder aerosol form.
Keywords: Cytotoxicity; Doxorubicin; Nanoparticles; Powder inhalation; Spray-freeze drying; Lung cancer cells

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