Injectable thermogelling
polymers have been recently investigated as novel adjuvants and delivery systems for next generation
vaccines. As research into natural and synthetic biocompatible
polymers progresses, the safety and biocompatibility of these compounds is of paramount importance. We have developed cationic pentablock copolymer (PBC)
vaccine adjuvants based on
Pluronic F127, a thermogelling triblock copolymer that has been approved by the FDA for multiple applications, and methacrylated poly(diethyl amino)ethyl
methacrylate outer blocks. These novel materials have been demonstrated to effectively create an
antigen depot, minimally impact
antigen stability, and enhance the immune response to
antigens (i.e., adjuvanticity) in mice. In this work, we investigated the safety and biocompatibility of the parent triblock
Pluronic gels and the cationic PBC
gels in mice. Histological analysis showed no
injection site reactions and no damage to the liver or kidneys was observed upon administering the block copolymer formulations. However, the
subcutaneous injection of a thermogelling
Pluronic solution induced increased levels of
lipids in the blood, with no further deleterious effects observed from the addition of the cationic outer blocks. This
hyperlipidemia resolved within 30 days after the administration of the
Pluronic formulation. To mitigate this adverse effect, the
vaccine adjuvant formulations were modified by adding poly(vinyl alcohol), which allowed gelation, while reducing the amount of
Pluronic in the formulation. This modified formulation abrogated the observed
hyperlipidemia and no adverse effects were observed in the serum through
biomarker analysis or at the injection site (i.e.,
inflammation) in comparison to the responses induced by administration of saline or
incomplete Freund's adjuvant. These studies provide a foundation to developing these
gels as adjuvants for next generation
vaccines. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1754-1762, 2019.