Abstract
Thermoresponsive gels have unique physicochemical properties that may enable more effective mucosal delivery of active compounds. The thermoresponsive gel (TRG) formulation developed by our group for sublingual delivery maintains fluid-like liquid properties at 2 °C–8 °C and forms a gel at the physiological temperature (~37 °C) within a few seconds. Here, we describe the preparation of a thermoresponsive gel vaccine formulation. Our preclinical studies with various antigens suggest that the mucoadhesive, adjuvanted TRG formulation enabled increased contact of the vaccine antigen with the mucosa, resulting in increased mucosal response(s) with a potential for antigen dose reduction.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Holmgren J, Svennerholm AM (2012) Vaccines against mucosal infections. Curr Opin Immunol 24(3):343–353
Kraan H, Vrieling H, Czerkinsky C, Jiskoot W et al (2014) Buccal and sublingual vaccine delivery. J Control Release 190(28):580–592
(2010) The Indian Pharmacopoeia. Ghaziabad, India: Ministry of Health and Public Welfare, Government of India, New Delhi
Mestecky J (1993) Saliva as a manifestation of the common mucosal immune system. Ann N Y Acad Sci 694:184–194
Ekstrom J, Khosravani N, Castagnola M, Messana I (2012) Saliva and the control of its secretion. In: Dysphagia, medical radiology. diagnostic imaging. Berlin: Springer.
White JA, Blum JS, Hosken NA, Marshak JO, Duncan L, Zhu C et al (2014) Serum and mucosal antibody responses to inactivated polio vaccine after sublingual immunization using a thermoresponsive gel delivery system. Hum Vaccin Immunother 10:3611–3621
Gonzalez-Mariscal L, Betanzos A, Nava P, Jaramillo BE (2003) Tight junction proteins. Progr Biophys Mol Biol 81:1–44
MatTek corporation (2012) Measurement of Transepithelial Electrical Resistance (TEER) and potential difference. MK-24-007-0051. Ashland, MA
Raymond CR, Paul JS, Sian CO (2006) Handbook of pharmaceutical excipients, 5th edn. American Pharmacists Association, Washington
Schmolka IR (1977) A review of block polymer surfactants. J Am Oil Chem Soc 54:110–116
Bonacucina G, Martelli S, Palmieri GF (2004) Rheological, mucoadhesive and release properties of Carbopol gels in hydrophilic cosolvents. Int J Pharm 282:115–130
Dow Chemical (1998) METHOCEL cellulose ethers. Technical handbook. Midland, MI
Norton EB, Lawson LB, Freytag LC, Clements JD (2011) Characterization of a mutant Escherichia coli heat-labile toxin, LT(R192G/L211A), as a safe and effective oral adjuvant. Clin Vaccine Immunol 18(4):546–551
El-Kamary SS, Cohen MB, Bourgeois AL, Van De Verg L, Bauers N et al (2013) Safety and immunogenicity of a single oral dose of recombinant double mutant heat-labile toxin derived from enterotoxigenic Escherichia coli. Clin Vaccine Immunol 20(11):1764–1770
Acknowledgement
This work was funded by grants from the Bill & Melinda Gates Foundation. The views expressed herein are solely those of the authors and do not necessarily reflect the views of the Gates Foundation.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Science+Business Media New York
About this protocol
Cite this protocol
Lal, M., White, J., Zhu, C. (2017). Preparing an Adjuvanted Thermoresponsive Gel Formulation for Sublingual Vaccination. In: Fox, C. (eds) Vaccine Adjuvants. Methods in Molecular Biology, vol 1494. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6445-1_11
Download citation
DOI: https://doi.org/10.1007/978-1-4939-6445-1_11
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-6443-7
Online ISBN: 978-1-4939-6445-1
eBook Packages: Springer Protocols