title: Formulation and cytotoxicity of doxorubicin nanoparticles carried by dry powder aerosol particles.
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 microm 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.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alta., Canada T6G 2N8.
authors.forename: Shirzad
authors.initials: S
authors.lastname: Azarmi
authors.forename: Xia
authors.initials: X
authors.lastname: Tao
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.forename: Zhaolin
authors.initials: Z
authors.lastname: Wang
authors.forename: Warren H
authors.initials: WH
authors.lastname: Finlay
authors.forename: Raimar
authors.initials: R
authors.lastname: Löbenberg
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Roa
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004337:Drug Carriers; D004659:Enbucrilate / Q000737:chemistry*; D005612:Freeze Drying; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018613:Microscopy, Confocal; D053758:Nanoparticles; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders; D013678:Technology, Pharmaceutical
chemical_list: D000336:Aerosols; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D011208:Powders; D004317:Doxorubicin; D004659:Enbucrilate