Aerosol delivery of liposomal all-trans-retinoic acid to the lungs

Purpose: To optimize the delivery of all-transretinoic acid (ATRA) to lung tissue, we determined the potential of vehiculating the drug in liposomes ( L-ATRA) and delivering it via aerosol. Liposomes may provide a means to pre vent local irritation of lung tissue and reduce pulmonary toxicity, prolong therapeutic levels and generate high drug concentrations at the tumor site s. Cumulatively, this would result in reduced systemic toxicity and enhance d drug efficacy. Methods: Previous studies have shown that liposomes can se rve as excellent carriers for otherwise poorly soluble ATRA. Delivery of AT RA to the lung tissue of mice was accomplished by nebulization of L-ATRA. T he liposomes in the aerosol were relatively uniform (309 +/- 138 nm), stabl e, and retained the drug well. Results: The drug was effectively delivered at high concentrations (10 +/- 2 mu g/g of tissue) to the lungs of mice and was retained for at least up to 96 h after a single exposure to L-ATRA aer osol. No appreciable levels of ATRA were detected in the blood or the liver of treated mice. The aerosol-delivered ATRA was biologically active as dem onstrated by its ability to induce the expression of tissue-type transgluta minase. Conclusion: Aerosol delivery of L-ATRA offers an effective way to d eliver high levels of ATRA to the lung without apparent pulmonary toxic eff ects.