Journal article
Microcontainers for protection of oral vaccines, in vitro and in vivo evaluation
Polymer Cell, Immunobiology and Biomimetics, Department of Health Technology, Technical University of Denmark1
Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics, Department of Health Technology, Technical University of Denmark2
Immunobiology and Biomimetics, Department of Health Technology, Technical University of Denmark3
Department of Health Technology, Technical University of Denmark4
University of Otago5
Research group for Nano-Bio Science, National Food Institute, Technical University of Denmark6
National Food Institute, Technical University of Denmark7
University of Copenhagen8
Nanoprobes, Drug Delivery and Sensing, Department of Health Technology, Technical University of Denmark9
Drug Delivery and Sensing, Department of Health Technology, Technical University of Denmark10
...and 0 moreOral vaccines are highly desirable due to simple logistics, mass vaccination potential and for mucosal immunity. Subunit vaccines are preferred due to high safety, but are inherently difficult to deliver orally, thus providing motivation for the use of advanced oral delivery systems. Polymeric devices in micrometer size (microcontainers) were tested here for this purpose.
Microcontainers were loaded with a vaccine consisting of spray dried cubosomes with OVA and Quil-A, and coated with a pH-sensitive lid for oral delivery to C57Bl/6 mice. The microcontainers were explored in vitro and in vivo for their potential as oral vaccine delivery system in an oral prime-boost setting and as an oral booster after a subcutaneously injected prime.
The pH of the stomach of C57Bl/6 mice was measured to be < 4.7 and it ranged from pH 5.8-7.1 in the small intestine, where the residence time of microcontainers was less than one hour. Eudragit® L100-55 was therefore chosen as lid material on the microcontainers as it remained stable in vitro at pH 4.7 and allowed release of the cubosomes within 30-60 min at pH 6.6, which simulated the mean pH of the distal half of the small intestine.
In vitro small angle x-ray scattering showed that cubosomes dissolved in small intestinal fluid when not confined in microcontainers but when loaded into microcontainers they were released as hexosomes. However, while microcontainers could protect and release particles with OVA and Quil-A within relevant time frames in vitro, an immune response was not elicited in vivo after oral administration.
Nonetheless, some effect was observed when the microcontainers were used to deliver oral boosters following a subcutaneous prime. This work indicates that oral vaccination with subunit vaccines has potential when combined with a parenteral prime and that oral delivery systems like microcontainers may be used to increase the potency of vaccines with low oral immunogenicity.
Language: | English |
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Year: | 2019 |
Pages: | 91-101 |
ISSN: | 18734995 and 01683659 |
Types: | Journal article |
DOI: | 10.1016/j.jconrel.2018.11.030 |
ORCIDs: | 0000-0001-9398-5344 , 0000-0002-7521-6020 , Nielsen, Line Hagner and Boisen, Anja |