The potential for production of freeze-dried oral vaccines using alginate hydrogel microspheres as protein carriers

• Published in: Journal of drug delivery science and technology Vol. 24; no. 2; pp. 178 - 184
• Main Authors: Hariyadi, D.M., Ma, Y., Wang, Y., Bostrom, T., Malouf, J., Turner, M.S., Bhandari, B., Coombes, A.G.A.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-01-2014
• Subjects: Alginate hydrogel microspheres; Bovine serum albumin; ESEM; In vitro release; Maltodextrin cryoprotectant; Oral vaccine; Protein; Maltodextrin cryoprotectant; Bovine serum albumin; ESEM; In vitro release; Oral vaccine; Alginate hydrogel microspheres; Protein
• ISSN: 1773-2247
• DOI: 10.1016/S1773-2247(14)50029-9

Oral administration of dry vaccine formulations is acknowledged to offer major clinical and logistical benefits by eliminating the cold chain required for liquid preparations. A model antigen, bovine serum albumin (BSA) was encapsulated in alginate microspheres using aerosolisation. Hydrated microspheres 25 to 65 μm in size with protein loading of 3.3 % w/w were obtained. Environmental scanning electron microscopy indicated a stabilizing effect of encapsulated protein on alginate hydrogels revealed by an increase in dehydration resistance. Freeze drying of alginate microspheres without use of a cryoprotectant resulted in fragmentation and subsequent rapid loss of the majority of the protein load in simulated intestinal fluid in 2 h, whereas intact microspheres were observed following freeze-drying of BSA-loaded microspheres in the presence of maltodextrin. BSA release from freeze-dried preparations was limited to less than 7 % in simulated gastric fluid over 2 h, while 90 % of the protein load was gradually released in simulated intestinal fluid over 10 h. SDS-PAGE analysis indicated that released BSA largely preserved its molecular weight. These findings demonstrate the potential for manufacturing freeze-dried oral vaccines using alginate microspheres.