TY - JOUR
T1 - Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release
AU - Tzeng, Stephany Y.
AU - Guarecuco, Rohiverth
AU - McHugh, Kevin J.
AU - Rose, Sviatlana
AU - Rosenberg, Evan M.
AU - Zeng, Yingying
AU - Langer, Robert
AU - Jaklenec, Ana
N1 - Funding Information:
This work was funded by the Bill and Melinda Gates Foundation ( OPP1095790 ). The authors would also like to thank Dr. James J. Norman, Dr. Adam M. Behrens, and Chase P. Kelley for their assistance with IPV stability assays and Dr. Adam M. Behrens and Dr. Shiran Ferber for their assistance with animal sample collection.
Publisher Copyright:
© 2016 The Authors. Published by Elsevier B.V.
PY - 2016/7/10
Y1 - 2016/7/10
N2 - Vaccines are a critical clinical tool in preventing illness and death due to infectious diseases and are regularly administered to children and adults across the globe. In order to obtain full protection from many vaccines, an individual needs to receive multiple doses over the course of months. However, vaccine administration in developing countries is limited by the difficulty in consistently delivering a second or third dose, and some vaccines, including the inactivated polio vaccine (IPV), must be injected more than once for efficacy. In addition, IPV does not remain stable over time at elevated temperatures, such as those it would encounter over time in the body if it were to be injected as a single-administration vaccine. In this manuscript, we describe microspheres composed of poly(lactic-co-glycolic acid) (PLGA) that can encapsulate IPV along with stabilizing excipients and release immunogenic IPV over the course of several weeks. Additionally, pH-sensitive, cationic dopants such as Eudragit E polymer caused clinically relevant amounts of stable IPV release upon degradation of the PLGA matrix. Specifically, IPV was released in two separate bursts, mimicking the delivery of two boluses approximately one month apart. In one of our top formulations, 1.4, 1.1, and 1.2 doses of the IPV serotype 1, 2, and 3, respectively, were released within the first few days from 50 mg of particles. During the delayed, second burst, 0.5, 0.8, and 0.6 doses of each serotype, respectively, were released; thus, 50 mg of these particles released approximately two clinical doses spaced a month apart. Immunization of rats with the leading microsphere formulation showed more robust and long-lasting humoral immune response compared to a single bolus injection and was statistically non-inferior from two bolus injections spaced 1 month apart. By minimizing the number of administrations of a vaccine, such as IPV, this technology can serve as a tool to aid in the eradication of polio and other infectious diseases for the improvement of global health.
AB - Vaccines are a critical clinical tool in preventing illness and death due to infectious diseases and are regularly administered to children and adults across the globe. In order to obtain full protection from many vaccines, an individual needs to receive multiple doses over the course of months. However, vaccine administration in developing countries is limited by the difficulty in consistently delivering a second or third dose, and some vaccines, including the inactivated polio vaccine (IPV), must be injected more than once for efficacy. In addition, IPV does not remain stable over time at elevated temperatures, such as those it would encounter over time in the body if it were to be injected as a single-administration vaccine. In this manuscript, we describe microspheres composed of poly(lactic-co-glycolic acid) (PLGA) that can encapsulate IPV along with stabilizing excipients and release immunogenic IPV over the course of several weeks. Additionally, pH-sensitive, cationic dopants such as Eudragit E polymer caused clinically relevant amounts of stable IPV release upon degradation of the PLGA matrix. Specifically, IPV was released in two separate bursts, mimicking the delivery of two boluses approximately one month apart. In one of our top formulations, 1.4, 1.1, and 1.2 doses of the IPV serotype 1, 2, and 3, respectively, were released within the first few days from 50 mg of particles. During the delayed, second burst, 0.5, 0.8, and 0.6 doses of each serotype, respectively, were released; thus, 50 mg of these particles released approximately two clinical doses spaced a month apart. Immunization of rats with the leading microsphere formulation showed more robust and long-lasting humoral immune response compared to a single bolus injection and was statistically non-inferior from two bolus injections spaced 1 month apart. By minimizing the number of administrations of a vaccine, such as IPV, this technology can serve as a tool to aid in the eradication of polio and other infectious diseases for the improvement of global health.
KW - Controlled release kinetics
KW - Drug delivery
KW - Single-administration vaccines
KW - Vaccine delivery
KW - Vaccine stability
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U2 - 10.1016/j.jconrel.2016.05.012
DO - 10.1016/j.jconrel.2016.05.012
M3 - Article
C2 - 27178811
AN - SCOPUS:84969505008
SN - 0168-3659
VL - 233
SP - 101
EP - 113
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -