Characterization of different vitamin E carriers intended for pulmonary drug delivery

Abstract

The targeted release of drugs intended for pulmonary delivery is a research field which has been so far rather unexploited but is currently becoming increasingly attractive. Liquid dispersions encapsulating vitamin E (liposomes, micelles, nano-emulsion, and solid lipid particles) were prepared using various methods based on membrane contactor. The dispersions were nebulized and aerodynamic characteristics of the generated aerosols were assessed using two different methods: laser light scattering and cascade impaction. When the laser diffraction technique was used, results showed that fine particle fractions (<5 μm) were 19, 29, 38 and 71% for solid lipid particles, micelles, nano-emulsion and liposomes, respectively. When the impaction method was applied, using a next generation pharmaceutical impactor operated at 30 l/min, results showed that fine particle fractions were 39, 78, 82 and 87% for solid lipid particles, micelles, nano-emulsion and liposomes, respectively. The differences observed between the results obtained from both methods confirm that the laser diffraction method is not always suitable for aerodynamic characterization of aerosols and should be validated against an impaction method. Nebulization of the drug-carrier systems led to an increase of their size most likely due to aggregation phenomena. The size was increased by a factor of 2-26 depending on the encapsulation system. The most important aggregation was obtained with nano-emulsion; the less one with solid lipid particles. The mass median aerodynamic diameter (MMAD) of the generated aerosols ranged from 1.76 to 6.10 μm. The application of a mathematical model, the Multiple-Path Particle Dosimetry (MPPD), for the prediction of the pulmonary deposit gave encouraging results. The rate of vitamin E able to reach the lung ranged from 37.6 (for the liposomes) to 51.6% (for the micelles). The obtained results showed that the different systems developed for vitamin E encapsulation were suitable to target the lung after pulmonary administration by nebulization.

Keywords: Aerosols; Drug-carrier; Lung deposit; Pulmonary administration; Vitamin E encapsulation.