Stabilization of tetanus toxoid encapsulated in PLGA microspheres.

Molecular Pharmaceutics
Wenlei Jiang, Steven P Schwendeman

Abstract

Delivery of vaccine antigens from controlled-release poly(lactic/glycolic acid) (PLGA) microspheres is a novel approach to reduce the number of antigen doses required for protection against infection. A major impediment to developing single-shot vaccines is encapsulated antigen instability during months of exposure to physiological conditions. For example, efforts to control neonatal tetanus in developing countries with a single-dose TT vaccine based on PLGA microspheres have been plagued by poor stability of the 150 kDa formaldehyde-detoxified protein antigen, tetanus toxoid (TT), in the polymer. We examined the denatured states of PLGA-encapsulated TT, revealing two primary TT instability mechanisms: (1) protein aggregation mediated by formaldehyde and (2) acid-induced protein unfolding and epitope damage. Further, we systematically identified excipients, which can efficiently inhibit TT aggregation and retain TT antigenicity under simulated deleterious conditions, i.e., elevated temperature and humidity. By employing these novel additives in the PLGA system, we report the slow and continuous release of high doses of TT for one month with retained antigen stability during bioerosion of PLGA.

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Citations

Jul 16, 2008·Pharmaceutical Research·Amy G Ding, Steven P Schwendeman
Nov 13, 2010·Pharmaceutical Research·Nishant Kumar Jain, Ipsita Roy
Mar 22, 2013·Pharmaceutical Research·Kashappa-Goud H DesaiSteven P Schwendeman
Apr 10, 2013·Pharmaceutical Research·Nishant Kumar JainIpsita Roy
Sep 29, 2011·AAPS PharmSciTech·Yun-Seok RheeHeidi M Mansour
Aug 13, 2015·Journal of Functional Biomaterials·Darren J Lee
Feb 26, 2009·Expert Opinion on Drug Delivery·Christopher F van der WalleMnv Ravi Kumar
Jul 28, 2012·Expert Opinion on Drug Delivery·Shirui MaoLuk Chiu Li
Jun 15, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Steven P SchwendemanAnna S Schwendeman
Jun 24, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Xiang YiAlexander V Kabanov
Oct 30, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Kashappa-Goud H Desai, Steven P Schwendeman
Nov 10, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Thejani E RajapaksaDavid D Lo
Aug 21, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Devika S ManickamAlexander V Kabanov
Feb 7, 2012·International Journal of Pharmaceutics·Jason C StanwickMolly S Shoichet
May 11, 2011·International Journal of Pharmaceutics·Aj BaxendaleL Illum
Dec 14, 2004·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lei Li, Steven P Schwendeman
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Apr 10, 2016·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Erika HammarlundMark K Slifka
Nov 14, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Masoud MalekiAlireza Talebzadeh
Oct 14, 2013·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Xiujun GaoNing Zhang

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