Amphotericin B lipid nanoemulsion aerosols for targeting peripheral respiratory airways via nebulization

Abstract

Amphotericin B (AmB) lipid nanoemulsions were prepared and characterized and their suitability for pulmonary delivery via nebulization was evaluated. AmB nanoemulsions were prepared by sonicating and vortexing the drug with two commercially available lipid nanoemulsions: the Intralipid ® or Clinoleic ®. Loading the nanoemulsions with the drug slightly increased the size of the lipid droplets and did not affect the zeta potential of the nanoemulsions. The loading efficiency of AmB was found to be 87.46 ± 2.21% in the Intralipid ® nanoemulsions and 80.7 ± 0.70% in the Clinoleic ® formulation. This respectively corresponded to 21.86 mg and 20.19 mg of AmB being successfully loaded in the nanoemulsions. On aerosolization using a Pari Sprint jet nebulizer, both nanoemulsions produced very high drug output which was approximately 90% for both formulations. Using the two-stage impinger, the Clinoleic ® emulsion had higher fine particle fraction (FPF) than the Intralipid ®, since the Clinoleic ® displayed higher deposition of AmB in the lower impinger stage (exceeding 80%), compared to 57% for the Intralipid ®. Overall, the ease of preparation of the AmB lipid nanoemulsions, along with their in vitro nebulization performance suggest that lipid nanoemulsions could be successful nanocarriers for delivery of AmB to the peripheral respiratory airways.