Uptake of all-trans retinoic acid-containing aerosol by inhalation to lungs in a guinea pig model system--a pilot study.
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.
Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, Tennessee 37208, USA.
Michael W
MW
Schäffer
Somdutta Sinha
SS
Roy
Shyamali
S
Mukherjee
David E
DE
Ong
Salil K
SK
Das
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D006168:Guinea Pigs; D008168:Lung / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D009330:Nebulizers and Vaporizers; D010865:Pilot Projects; D054840:Retinol-Binding Proteins, Cellular / Q000378:metabolism; D014212:Tretinoin / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000336:Aerosols; D000970:Antineoplastic Agents; D015415:Biomarkers; D054840:Retinol-Binding Proteins, Cellular; D014212:Tretinoin