Preparation of liposomes: a novel application of microengineered membranes - investigation of the process parameters and application to the encapsulation of vitamin E
Résumé
Liposomes with a mean size of 59-308 nm suitable for pulmonary drug delivery were prepared by the ethanol injection method using nickel microengineered flat disc membranes with a uniform pore size of 540 mm and a pore spacing of 80 or 200 mm. An ethanolic phase containing 20-50 mg ml(-1) phospholipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or Lipoid (R) E80), 5-12.5 mg ml(-1) stabilizer (cholesterol, stearic acid or cocoa butter), and 0 or 5 mg m(-1) vitamin E was injected through the membrane into an agitated aqueous phase at a controlled flux of 142-355 l m(-2) h(-1) and a shear stress on the membrane surface of 0.80-16 Pa. The mean particle size obtained under optimal conditions was 84 and 59 nm for Lipoid E80 and POPC liposomes, respectively. The particle size of the prepared liposomes increased with an increase in the pore size of the membrane and decreased with an increase in the pore spacing. Lipoid E80 liposomes stabilized by cholesterol or stearic acid maintained their initial size within 3 months. A high entrapment efficiency of 99.87% was achieved when Lipoid E80 liposomes were loaded with vitamin E. Transmission electron microscopy images revealed spherical multi-lamellar structure of vesicles. The reproducibility of the developed fabrication method was high.