Poloxamer 407‐chitosan grafted thermoresponsive hydrogels achieve synchronous and sustained release of antigen and adjuvant from single‐shot vaccines

Abstract

Sustained-release vaccine delivery systems may enhance the immunogenicity of subunit vaccines and reduce the need for multiple vaccinations. The aim of this study was to develop a thermoresponsive hydrogel using poloxamer 407-chitosan (CP) grafted copolymer as a delivery system for single-shot sustained-release vaccines. The CP copolymer was synthesized using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide and N-hydroxysuccinimide chemistry. The CP copolymer was a free flowing solution at ambient temperature and transformed rapidly into a gel at body temperature. The hydrogels were loaded with vaccine antigen and adjuvants or the vaccine components were encapsulated in poly (lactic-co-glycolic acid) nanoparticles in order to ensure synchronous release. The CP hydrogels were stable for up to 18 days in vitro. Release of both nanoparticles and the individual components was complete, with release of the individual components being modulated by incorporation into nanoparticles. In vivo, a single dose of CP hydrogel vaccine induced strong, long lasting, cellular and humoral responses that could protect against the development of tumors in a murine melanoma model.

Vaccine implants: current status and recent advancements

“…Physical mixtures of polymers are often difficult to formulate at physiological pH and suffer from poor aqueous stability, therefore, grafted copolymers have also been developed. A temperature responsive poloxamer 407-chitosan (CP) grafted copolymer hydrogel single-shot vaccine has been recently reported [13]. Here, a CP polymer solution containing OVA and the adjuvants MPL and Quil A was easily injectable at room temperature and rapidly transformed into a gel depot at body temperature.…”

“…Unlike most drug implants, vaccine implants usually require the relatively short-term release of vaccine components in order to induce potent immune responses while avoiding tolerance (low doses of antigen for an extended period of time) or sequestration and/or deletion (higher amounts of antigen over an extended period of time) of lymphocytes [12]. For example, implants that mimic a natural acute infection with the release of antigen in an immunogenic form over a period of 10-14 days would be optimal [13]. In this review, we examine the potential of vaccine implants and describe the different types of implantation strategies being used and developed to deliver vaccines.…”

Novel thermoresponsive polymer outperforming Pluronic® F127

“…As previously mentioned, the synthesis and the applications of thermoresponsive polymers have been extensively reported. [16][17][18][19][20][21][22][23][24][25][26][27][28] Among these, poloxamer P407 is the most commonly used thermoresponsive polymer, owing to its commercial availability. 21,29,30 This copolymer is a member of the family of Pluronics®, which are ABA triblock copolymers with A and B units being ethylene glycol (EG) and propylene glycol (PG), respectively, i.e.…”

The sixth revolution in pediatric vaccinology: immunoengineering and delivery systems

“…Activation of the inflammasome through cytosolic NOD-like receptors can lead to a self-adjuvant effect by the nanoparticle vehicle itself that promotes adaptive immunity (27)(28)(29). Lastly, nanoparticles containing vaccines can be used to control the duration of delivery through synchronous and sustained release of antigens and adjuvants (30,31).…”

“…Delivery kinetics can be further modified using strategies such as incorporating nanoparticles into hydrogels or intradermal microneedle delivery systems (30)(31)(32). These sustained release systems can allow for the development of single dose vaccines (33).…”