Optimization of the Preparation Process for an Oral Phytantriol-Based Amphotericin B Cubosomes

Abstract

In order to develop an oral formation of Amphotericin B (AmB) using phytantriol- (PYT-) based cubosomes with desirable properties, homogenization conditions were firstly investigated to determine their effects on the morphological and dimensional characteristics of cubosomes. Under the optimized homogenization conditions of 1200 bar for 9 cycles, cubosomes with reproducible, narrow particle size distribution and a mean particle size of 256.9 nm ± 4.9 nm were obtained. The structure of the dispersed cubosomes was revealed by SAXS (small-angle X-ray scattering) and Cryo-TEM (cryogenic transmission electron microscopy) as a bicontinuous cubic liquid crystalline phase with Pn3m geometry. To overcome the poor drug solubility and increase the drug-loading rate, a solubilization method was firstly used to develop cubosomes containing AmB. The encapsulation efficiency determined by HPLC assay was<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mn>87.8</mml:mn><mml:mi>%</mml:mi><mml:mo>±</mml:mo><mml:mn>3.4</mml:mn><mml:mi>%</mml:mi></mml:mrow></mml:math>, and UV spectroscopy and stability studies in simulated gastric fluids further confirmed that AmB was successfully encapsulated in cubosomes.