TY - JOUR
T1 - Mucoadhesive wafers composed of binary polymer blends for sublingual delivery and preservation of protein vaccines
AU - Hanson, Samuel M.
AU - Singh, Shailbala
AU - Tabet, Anthony
AU - Sastry, K. Jagannadha
AU - Barry, Michael
AU - Wang, Chun
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/2/10
Y1 - 2021/2/10
N2 - 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.
AB - 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.
KW - Mucoadhesive polymer
KW - Sublingual delivery
KW - Vaccine delivery
KW - Vaccine stabilization
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U2 - 10.1016/j.jconrel.2020.12.029
DO - 10.1016/j.jconrel.2020.12.029
M3 - Article
C2 - 33358974
AN - SCOPUS:85098662602
SN - 0168-3659
VL - 330
SP - 427
EP - 437
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -