title: Distribution of effervescent inhalable nanoparticles after pulmonary delivery: an in vivo study.
abstract: BACKGROUND
  Effervescent inhalable nanoparticles (NPs) have previously been shown to be a promising alternative to conventional lung cancer treatment in animals. This study investigates the biodistribution of effervescent inhalable NPs after a single dose administration via pulmonary route in lung cancer-bearing mice.
  
  
  RESULTS
  Whole-body autoradiography and confocal laser-scanning microscopy (CLSM) were used to investigate the distribution of inhalable NPs loaded in an effervescent microcarrier. Inhalable doxorubicin-loaded NPs were tagged with 14C for whole-body autoradiography, or with fluorescein isothiocyanate for CLSM imaging. After pulmonary delivery, NPs were widely disseminated in the lungs with a long retention time (24 h). The heart was radioactivity free at all time points of the study. CLSM images showed that inhalable NPs were taken up by cells and that doxorubicin was released to the cell nuclei.
  
  
  CONCLUSIONS
  This is the first study to investigate the distribution of inhalable NPs in a lung cancer-bearing animal model. Inhalable NPs achieved deep lung deposition, were actively released from microcarrier particles, spread to different parts of the lung and released doxorubicin in vivo. These NP characteristics contribute to the efficacy of effervescent inhalable NPs as a lung cancer treatment.
authors: Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2N8, Canada.
authors: M H D Kamal
authors: MH
authors: Al-Hallak
authors: Muhammad K
authors: MK
authors: Sarfraz
authors: Shirzad
authors: S
authors: Azarmi
authors: Wilson H
authors: WH
authors: Roa
authors: Warren H
authors: WH
authors: Finlay
authors: Claude
authors: C
authors: Rouleau
authors: Raimar
authors: R
authors: Löbenberg
mesh_terms: D021581:Active Transport, Cell Nucleus; D000280:Administration, Inhalation; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D001345:Autoradiography; D002250:Carbon Radioisotopes; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D003487:Cyanoacrylates / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers; D004339:Drug Compounding; D004659:Enbucrilate; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D053758:Nanoparticles; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D051598:Whole Body Imaging / Q000379:methods
chemical_list: D000903:Antibiotics, Antineoplastic; D002250:Carbon Radioisotopes; D003487:Cyanoacrylates; D004337:Drug Carriers; D005456:Fluorescent Dyes; D004317:Doxorubicin; D004659:Enbucrilate; D016650:Fluorescein-5-isothiocyanate