Cellulose acetate phthalate microparticles containing Vibrio cholerae: steps toward an oral cholera vaccine

Abstract

Oral cholera vaccine (OCV) has been recommended in some endemic areas and epidemic situations since 1999. Although safe and effective vaccines are currently on the market, the burden of transport and storage remains an issue. Herein, we report an approach to develop an alternative OCV in the form of a gastro-resistant powder. Heat-killed Vibrio cholerae (VC) was encapsulated with a spray-drying technique at different temperatures. Cellulose acetate phthalate (Aquacoat® CPD) was chosen as the core polymer and the addition of alginate was studied. The microparticles (MPs) produced were characterized by surface morphology, particle size, drug loading, antigenicity and gastro resistance. The MPs obtained were 6 µm in size and had appropriate drug content, ranging from 8.16 to 8.64%. Furthermore, antigenicity was maintained, never dropping below 85%, and enteric properties were achieved for all the formulations. Next, an in vivo study was carried out with Aquacoat® CPD MP prepared at 80 °C with and without alginate. Two different doses were assayed, 30 and 60 mg, and compared to the VC suspension. The evoked immune responses showed that alginate containing MPs, especially at the 30 mg dose, displayed values that were very similar to those of VC. In conclusion, spray-dried alginate VC MPs seem to be a promising step toward a powder-form cholera vaccination.

• Cellulose acetate phthalate
• cholera vaccines
• enteric microparticles
• spray drying

Acknowledgements

M. Pastor would like to thank the Basque Government (Department of Education, Universities and Research) for the fellowship grant. Technical and human support provided by SGIker (UPV/EHU, MICINN, GV/EJ, ERDF and ESF) is gratefully acknowledged. The authors would like to thank FMC Biopolymer and Vertellus® for kindly providing Aquacoat® CPD and triethylcitrate, respectively.