Nebulization of niosomal all-trans-retinoic acid: an inexpensive alternative to conventional liposomes

Abstract

In this study we have demonstrated the potential of encapsulating all-trans-retinoic acid (ATRA) in niosomes and delivering it as an inhaled aerosol. Niosomes may provide a means to reduce the toxicity of ATRA and alter the pharmacokinetics in a manner similar to liposomes. In addition, the low cost of the surfactants used for preparing niosomes and their greater stability compared with liposomes makes them an attractive alternative. Various nonionic surfactants were used to achieve optimum encapsulation and nebulization efficiencies, and the best formulations were obtained with combinations of (Span 20+Tween 80) and (Span 60+Tween 80) using an ATRA concentration of 1 mg/ml. The aerosol produced with the selected niosomal formulations upon nebulization in PARI LC STAR nebulizers driven by a Pulmo-Aide compressor was subsequently analyzed for the determination of size distribution and entrapment efficiencies on each stage of an Anderson cascade impactor operated in a manner that avoids spurious sizing due to droplet evaporation. Mass median aerodynamic diameters (MMADs) of 3.7±0.3 and 3.58±0.03 μm, geometric standard deviation (GSD) values of 1.59±0.17 and 1.51±0.01 and entrapment efficiencies well above 50% were obtained for the optimized formulations. The results are very encouraging and offer an alternative approach to the respiratory delivery of ATRA by aerosolization.