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

Exp Lung Res. 2010 Dec;36(10):593-601.
Schäffer MW, Roy SS, Mukherjee S, Ong DE, Das SK.
Exp Lung Res. 2010 Dec;36(10):593-601.
Applicazione di aerosol di acido all-trans retinoico (ATRA) induce una espressione dose-dipendente di una proteina legata al retinolo cellulare 1 (CRBP-1) nel polmone, senza apparenti effetti collaterali nocivi.
ATRA areosol/CRBP-1.

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 32 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.