title: Microcontainers as an oral delivery system for spray dried cubosomes containing ovalbumin.
abstract: The purpose of this study was to prepare cubosomes encapsulating the model antigen ovalbumin (OVA) via spray drying, and to characterise such cubosomes with a view for their potential application in oral vaccine delivery. Furthermore the cubosome formulation was loaded into polymeric microcontainers intended as an oral drug delivery system. The cubosomes consisted of commercial glyceryl monooleate, Dimodan®, containing OVA and were surrounded with a dextran shell prepared by spray drying. Cryo-TEM was used to confirm that cubosomes were formed after hydration of the spray dried precursor powder. The precursor powder had a mean particle size of 1.3±0.1μm, whereas the mean diameter of the dispersed cubosomes was 282±7nm (PDI: 0.18) measured by dynamic light scattering. 8.5±0.3% (w/w) of OVA was present in the cubosome powder and OVA was found released slowly over the first 70h, followed by a more rapid release. Total release of 47.9±2.8% of loaded OVA occurred over 96h in a buffer at pH 6.8. When the powder was filled into microcontainers, and the opening covered with the pH sensitive polymer Eudragit S100, the pH sensitive 'lid' was intact at gastric pH, but release of OVA from the cubosomes and microcontainers occurred at pH 6.8, releasing 44.1±5.6% of the OVA in 96h. Small-angle X-ray scattering (SAXS) revealed that the 'dry' particles possessed an internal ordered lipid structure (lamellar and inverse micellar phase) by virtue of a small amount of residual water, and after hydration in buffer at pH 6.8, the particles formed the hexagonal inverse cubic phases, thereby indicating that cubosomes were formed when released from microcontainers.
authors.affiliation: Department of Micro and Nanotechnology, Technical University of Denmark, Kgs. Lyngby, Denmark. Electronic address: lihan@nanotech.dtu.dk.
authors.forename: Line Hagner
authors.initials: LH
authors.lastname: Nielsen
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Boyd
authors.affiliation: Department of Micro and Nanotechnology, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Anja
authors.initials: A
authors.lastname: Boisen
mesh_terms: D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D003890:Desiccation / Q000379:methods; D003911:Dextrans / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D005989:Glycerides / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008823:Micelles; D010047:Ovalbumin / Q000008:administration & dosage*; D010316:Particle Size; D011208:Powders; D053838:Scattering, Small Angle; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D003692:Delayed-Action Preparations; D003911:Dextrans; D005989:Glycerides; D008055:Lipids; D008823:Micelles; D011208:Powders; D014867:Water; D010047:Ovalbumin; C005953:monoolein
keywords: Lipid self-assembly; Micro devices; Oral drug delivery; Oral vaccine delivery; Particulates; Spray drying