The enhancing effect of ε-polylysine on the immunization delivery efficiency of pluronic mixed micelles

Abstract To investigate the potential of Pluronic as an antigen delivery carrier and to clarify the role of ε-polylysine (ε-PL) in antigen delivery, ovalbumin (OVA) loaded Pluronic micelles (PM) and ε-PL-modified Pluronic micelles (ε-PM) were developed. They were prepared using the direct dissolution method and characterized by particle size distribution, Zeta potential, encapsulation efficiency, and structural analysis. The biocompatibility of the carriers and the efficiency mechanism of protein delivery into cells were evaluated through cell experiments. Nasal immunization was performed in mice to assess the immune-enhancing effects and safety of ε-PM in vivo. The particle sizes of PM and ε-PM were ~30 nm. After modification with ε-PL, the Zeta potential shifted from negative to positive. Both carriers exhibited good biocompatibility. PM and ε-PM were effectively taken up by RAW264.7 cells, with ε-PM showing enhanced uptake and subsequent transport to the perinuclear region. The primary cellular uptake pathway for PM and ε-PM was caveolin-mediated endocytosis. In vivo, ε-PM more effectively activated local and systemic humoral immune responses, without causing noticeable inflammatory responses or tissue damage. This study demonstrated that Pluronic micelles have the potential to serve as nano-adjuvants for subunit vaccines and that ε-PL can effectively enhance antigen delivery efficiency.