Abstract
The objective of this study is to develop a simple biopolymer platform of mucoadhesive wafers that enables effective sublingual delivery and preservation of protein vaccines. The wafers were composed of a series of binary polymer blends of carboxymethylcellulose (CMC) and alginate (ALG). Varying the ratio between CMC and ALG resulted in wafers with different microstructure, mechanical properties, disintegration time, and release kinetics of model compounds. Wafers with high CMC content were highly mucoadhesive to sublingual mucosal tissue and could withstand extensive washing, leading to improved protein permeation into the tissue. On the other hand, wafers with high ALG content were not only mechanically robust, but also able to protect a model enzyme (β-galactosidase) against lyophilization and heat challenge. HIV gp140 protein loaded in wafers of the optimal composition could be stored and transported without cold chain, while maintaining antigen-specific immunogenicity after sublingual vaccination in mice. These findings established that the CMC/ALG binary blend polymer wafers have the potential to improve the sublingual delivery and storage stability of protein-based vaccines.
Original language | English (US) |
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Pages (from-to) | 427-437 |
Number of pages | 11 |
Journal | Journal of Controlled Release |
Volume | 330 |
DOIs | |
State | Published - Feb 10 2021 |
Bibliographical note
Funding Information:This work was funded by a grant from the Minnesota Partnership for Biotechnology and Medical Genomics . We thank Dr. Paul Iazzio for kindly providing the porcine sublingual tissue. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC Program . C.W. dedicates this paper to Prof. Jindřich Kopeček.
Publisher Copyright:
© 2020 Elsevier B.V.
Keywords
- Mucoadhesive polymer
- Sublingual delivery
- Vaccine delivery
- Vaccine stabilization
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.