Improved respiratory delivery of the anticancer drugs, camptothecin and paclitaxel, with 5% CO2-enriched air: pharmacokinetic studies.
OBJECTIVE
To increase pulmonary deposition of anticancer liposome aerosols in mice by modulation of respiratory physiology through the addition of 5% CO2 to the air source used to generate the aerosols. Breathing CO2-enriched aerosol increases pulmonary ventilation with concurrent increased deposition of inhaled particles.


METHODS
Dilauroylphosphatidylcholine liposome formulations of two anticancer drugs, paclitaxel (PTX) and camptothecin (CPT), were investigated. The aerosol droplet size was measured using an Andersen cascade impactor. Drug concentrations in aerosol droplet fractions and tissues were determined by HPLC analysis. ICR mice were exposed to each liposome aerosol for 30 min. For each drug, one group of mice inhaled the drug-liposome aerosol generated with a mixture of 5% CO2 in air and another group inhaled the drug-liposome aerosols produced with normal air. Tissue distribution and pharmacokinetics were determined for both drug delivery systems.


RESULTS
Significantly higher concentrations of PTX and CPT were found in organs of mice exposed to 5% CO2-air aerosols compared to organs of mice exposed to normal air aerosols. The highest concentrations of drug were detected in the lungs and were two- to fourfold higher with 5% CO2-air aerosols than with aerosols generated with normal air. Higher concentrations were also detected in liver, spleen, kidneys, blood, and brain.


CONCLUSIONS
5% CO2 enrichment of air increased respiratory tract deposition of inhaled aerosol particles containing PTX and CPT.
Koshkina
N V
NV
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA. koshkina@bcm.tmc.edu
Knight
V
V
Gilbert
B E
BE
Golunski
E
E
Roberts
L
L
Waldrep
J C
JC
D000280:Administration, Inhalation; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D008081:Liposomes; D051379:Mice; D008813:Mice, Inbred ICR; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D002245:Carbon Dioxide; D017239:Paclitaxel; D002166:Camptothecin