Spray dried cubosomes with ovalbumin and Quil-A as a nanoparticulate dry powder vaccine formulation

TY - JOUR

T1 - Spray dried cubosomes with ovalbumin and Quil-A as a nanoparticulate dry powder vaccine formulation

AU - von Halling Laier, Christoffer

AU - Gibson, Blake

AU - van de Weert, Marco

AU - Boyd, Ben J

AU - Rades, Thomas

AU - Boisen, Anja

AU - Hook, Sarah

AU - Nielsen, Line Hagner

N1 - Copyright © 2018 Elsevier B.V. All rights reserved.

PY - 2018/10/25

Y1 - 2018/10/25

N2 - Subunit vaccine formulations are often produced as liquid dispersions through complicated processes. It is desirable, however, to have simple, cheap and up-scalable methods to produce nanoparticulate subunit vaccines in powder form. Here, a simple single-step spray drying process for production of powder cubosome precursors with the model antigen ovalbumin (OVA) and the adjuvant Quil-A is presented. The cubosomes were characterized in vitro and evaluated in vivo by subcutaneous and oral administration for their potential as a vaccine formulation. Hydrated cubosomes had average particle size of 257 ± 8 nm and zeta potential of −18.0 ± 0.6 mV. The powder contained 10.6 ± 0.7% w/w OVA prior to hydration, of which 65 ± 1% was released within the first 20 min in 9.5 mM PBS at pH 7.3, with the remaining OVA gradually released over the following 24 h. Immunization with cubosomes resulted in significantly stronger antigen-specific serum IgG responses (p < 0.01), CD8+ T cell expansion (p < 0.0001) and target T cell killing compared to controls when given s.c., and was ineffective orally. This study shows that spray drying is a suitable method for producing nanoparticulate vaccine formulations in dry powder form.

AB - Subunit vaccine formulations are often produced as liquid dispersions through complicated processes. It is desirable, however, to have simple, cheap and up-scalable methods to produce nanoparticulate subunit vaccines in powder form. Here, a simple single-step spray drying process for production of powder cubosome precursors with the model antigen ovalbumin (OVA) and the adjuvant Quil-A is presented. The cubosomes were characterized in vitro and evaluated in vivo by subcutaneous and oral administration for their potential as a vaccine formulation. Hydrated cubosomes had average particle size of 257 ± 8 nm and zeta potential of −18.0 ± 0.6 mV. The powder contained 10.6 ± 0.7% w/w OVA prior to hydration, of which 65 ± 1% was released within the first 20 min in 9.5 mM PBS at pH 7.3, with the remaining OVA gradually released over the following 24 h. Immunization with cubosomes resulted in significantly stronger antigen-specific serum IgG responses (p < 0.01), CD8+ T cell expansion (p < 0.0001) and target T cell killing compared to controls when given s.c., and was ineffective orally. This study shows that spray drying is a suitable method for producing nanoparticulate vaccine formulations in dry powder form.

U2 - 10.1016/j.ijpharm.2018.08.036

DO - 10.1016/j.ijpharm.2018.08.036

M3 - Journal article

C2 - 30134183

SN - 0378-5173

VL - 550

SP - 35

EP - 44

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

IS - 1-2

ER -