Preparation and characterization of diphtheria toxoid-loaded elastic vesicles for transcutaneous immunization.
The objective was to develop surfactant-based vesicle formulations containing diphtheria toxoid (DT) for transcutaneous immunization. Formulation variables were molar ratio of the surfactants (sucrose-laurate ester, octaoxyethylene-laurate ester, and sodium bistridecyl sulfosuccinate), DT concentration, pH, and ionic strength. The formulations were characterized by visual inspection, dynamic light scattering and zeta potential measurements. DT loading efficiency and capacity of the vesicle formulations were studied by protein assay and enzyme-linked immunosorbent assay. DT-containing vesicle formulations were optimized for colloidal stability. The pH had a dramatic effect on DT-vesicle association: at pH 4.5 > 70% of the protein was associated with the vesicles, vs. < 20% at pH 5.0. By varying the ionic strength of the buffer, we revealed that hydrophobic interactions play an important role in the association. DT-vesicles formulated at pH 4.5 were stable and showed high association of DT with preserved antigenicity, and are therefore excellent candidates for future in vivo studies.
Ding
Zhi
Z
Division of Drug Delivery Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
Bivas-Benita
Maytal
M
Hirschberg
Hoang
H
Kersten
Gideon F A
GF
Jiskoot
Wim
W
Bouwstra
Joke A
JA
D002850:Chromatography, Gel; D004168:Diphtheria Toxoid / Q000008:administration & dosage*; D004337:Drug Carriers; D004591:Electrophoresis, Polyacrylamide Gel; D006863:Hydrogen-Ion Concentration; D007279:Injections, Subcutaneous; D009994:Osmolar Concentration; D010316:Particle Size; D013050:Spectrometry, Fluorescence
D004168:Diphtheria Toxoid; D004337:Drug Carriers