Surface hydrophobicity of microparticles modulates adjuvanticity

Polymeric microparticles are promising adjuvants and they exhibit various physicochemical characteristics that can regulate the immune response, including hydrodynamic size, morphology, and surface properties, among others. Surface hydrophobicity is also a key microparticle characteristic, but how it affects microparticle adjuvanticity remains unknown. To study the correlation between microparticle hydrophobicity and adjuvanticity in-depth, we prepared poly(d,l-lactic acid) (PLA)-, poly(d,l-lactic-co-glycolic acid) (PLGA)-, and poly(monomethoxypolyethylene glycol-co-d,l-lactide) (mPEG-PLA, PELA)-based microparticles by premix membrane emulsification, which were similar in size and morphology but differed in surface hydrophobicity. We then systematically evaluated their ability to induce immune responses in vitro and in vivo. Increased surface hydrophobicity on PLA-based microparticles greatly promoted antigen internalization into dendritic cells (DCs) as well as MHC II and CD86 expression on DCs in vitro. Similarly, in vivo studies showed that increased microparticle surface hydrophobicity significantly elevated cytokine secretion levels by splenocytes harvested from vaccinated mice. Adhesion force measurements confirmed that increased surface hydrophobicity enhanced the physical interaction between microparticles and cell membranes, a condition favorable for promoting microparticle internalization into cells. Taken together, these results indicated that microparticle hydrophobicity is an important factor that determines the magnitude of immune responses elicited by vaccination with different particulate systems.