Evaluating and optimizing oral formulations of live bacterial vaccines using a gastro-small intestine model

de Barros, J. M.S., Costabile, A., Charalampopoulos, D. ORCID: https://orcid.org/0000-0003-1269-8402, Khutoryanskiy, V. V. ORCID: https://orcid.org/0000-0002-7221-2630 and Edwards, A. D. ORCID: https://orcid.org/0000-0003-2369-989X (2016) Evaluating and optimizing oral formulations of live bacterial vaccines using a gastro-small intestine model. European Journal of Pharmaceutics and Biopharmaceutics, 102. pp. 115-122. ISSN 0939-6411 doi: 10.1016/j.ejpb.2016.03.010

Abstract/Summary

Gastrointestinal (GI) models that mimic physiological conditions in vitro are important tools for developing and optimizing biopharmaceutical formulations. Oral administration of live attenuated bacterial vaccines (LBV) can safely and effectively promote mucosal immunity but new formulations are required that provide controlled release of optimal numbers of viable bacterial cells, which must survive gastrointestinal transit overcoming various antimicrobial barriers. Here, we use a gastro-small intestine gut model of human GI conditions to study the survival and release kinetics of two oral LBV formulations: the licensed typhoid fever vaccine Vivotif comprising enteric coated capsules; and an experimental formulation of the model vaccine Salmonella Typhimurium SL3261 dried directly onto cast enteric polymer films and laminated to form a polymer film laminate (PFL). Neither formulation released significant numbers of viable cells when tested in the complete gastro-small intestine model. The poor performance in delivering viable cells could be attributed to a combination of acid and bile toxicity plus incomplete release of cells for Vivotif capsules, and to bile toxicity alone for PFL. To achieve effective protection from intestinal bile in addition to effective acid resistance, bile adsorbent resins were incorporated into the PFL to produce a new formulation, termed BR-PFL. Efficient and complete release of 4.4x107 live cells per dose was achieved from BR-PFL at distal intestinal pH, with release kinetics controlled by the composition of the enteric polymer film, and no loss in viability observed in any stage of the GI model. Use of this in vitro GI model thereby allowed rational design of an oral LBV formulation to maximize viable cell release.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/58447
Identification Number/DOI	10.1016/j.ejpb.2016.03.010
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) > Thermal Analysis (CAF) Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Pharmaceutics Research Group Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Food Research Group
Publisher	Elsevier
Download/View statistics	View download statistics for this item