Inhalable nanoparticles, a non-invasive approach to treat lung cancer in a mouse model.
Doxorubicin-loaded nanoparticles (NPs) were incorporated into inhalable effervescent and non-effervescent carrier particles using a spray-freeze drying technique. The prepared inhalable powders were tested in a tumor bearing Balb/c mouse model. Control mice were treated with blank inhalable NPs, inhalable lactose powder containing free doxorubicin, and intravenous injections of a suspension of doxorubicin NPs, doxorubicin solution, or saline solution. The survival of treatment groups was plotted with Kaplan-Meier curves. Animals treated with inhalable effervescent nanoparticle powder containing 30μg doxorubicin showed a highly significant improvement in survival compared to all other treatment groups. Mice in control groups treated with doxorubicin solution or doxorubicin NPs as intravenous injection, died in less than 50 days. Inhalable free doxorubicin showed high cardiac toxicity. Pathological samples showed large tumor masses in the lungs of animals not treated or treated with i.v. injections of doxorubicin NPs or doxorubicin solution. The lungs of animals treated with inhalable effervescent doxorubicin NPs showed fewer and much smaller tumors compared to the control groups, as visualized by MRI imaging which confirmed the observed pathology results. The present study demonstrates that inhalable effervescent doxorubicin NPs are an effective way to treat lung cancer. This non-invasive route of administration might change the way lung cancer is treated in the future.
Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB, Canada T6G 1Z2.
Wilson H
WH
Roa
Shirzad
S
Azarmi
M H D Kamal
MH
Al-Hallak
Warren H
WH
Finlay
Anthony M
AM
Magliocco
Raimar
R
Löbenberg
D000280:Administration, Inhalation; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D004317:Doxorubicin