Uptake of all-trans retinoic acid-containing aerosol by inhalation to lungs in a guinea pig model system--a pilot study.

TitleUptake of all-trans retinoic acid-containing aerosol by inhalation to lungs in a guinea pig model system--a pilot study.
Publication TypeJournal Article
Year of Publication2010
AuthorsSchäffer MW, Sinha RS, Mukherjee S, Ong DE, Das SK
JournalExp Lung Res
Volume36
Issue10
Pagination593-601
Date Published2010 Dec
ISSN1521-0499
KeywordsAdministration, Inhalation, Aerosols, Animals, Antineoplastic Agents, Biomarkers, Blotting, Western, Chromatography, High Pressure Liquid, Guinea Pigs, Lung, Male, Models, Animal, Nebulizers and Vaporizers, Pilot Projects, Retinol-Binding Proteins, Cellular, Tretinoin
Abstract

Systemic therapies with retinoic acid (RA) can result in toxic side effects without yielding biologically effective levels in target tissues such as lung. The authors adapted a PARI LC Star nebulizer to create a tubular system for short-term inhalation treatment of guinea pigs using a water-miscible formulation of all-trans RA (ATRA) or vehicle. Based on the initial average weight, animals received an estimated average ATRA doses of either 0.32 mg·kg(-1) (low dose, 1.4 mM), or 0.62 mg·kg(-1) (medium dose, 2.8 mM), or 1.26 mg·kg(-1) (high dose, 5.6 mM) 20 minutes per day for 6 consecutive days. This system led to a rise of ATRA levels in lung, but not liver or plasma. Cellular lung levels of retinol, retinyl palmitate, and retinyl stearate also appeared to be unaffected (245.6 ± 10.7, 47.4 ± 3.4, and 132.8 ± 7.7 ng·g(-1) wet weight, respectively). The application of this aerosolized ATRA also induced a dose-dependent protein expression of the cellular retinol-binding protein 1 (CRBP-1) in lung, without apparent harmful side effects.

DOI10.3109/01902141003790155
Alternate JournalExp. Lung Res.
PubMed ID21043991
PubMed Central IDPMC3058486
Grant List1R03 HL095419-01A1 / HL / NHLBI NIH HHS / United States
R03 HL095419 / HL / NHLBI NIH HHS / United States
R03 HL095419-01A1 / HL / NHLBI NIH HHS / United States
R03 HL095419-02 / HL / NHLBI NIH HHS / United States