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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., Methods & 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., Conclusion: 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.

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., (Copyright © 2010 Elsevier B.V. All rights reserved.)

A bio-polyelectrolyte microshell composed of alginate sodium (ALG) and chitosan (CHI) was fabricated by electrostatic layer-by-layer (LbL) self-assembly technique. The resulting ALG-CHI microshells were found to be able to effectively load anti-cancer drug doxorubicin (DOX) in the interior of the shells under modest conditions without addition of other reagents, as demonstrated by confocal laser scanning microscopy (CLSM). The mass of DOX loaded in one capsule of four alginate/chitosan layers (i.e. the volume V=2.5x10(-10) cm3) is calculated as ca. 1.4x10(-13) g, which corresponds to 1.5x10(8) DOX molecules. Also, the release of DOX in the shells is dependent on the number of assembled layers of the shells. Colorimetric XTT cell viability assay results showed that the DOX-loaded microshells at high concentrations tested could kill cancer cells more efficiently than free-DOX alone.

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.