Tolerizing effect of PLGA nanoparticles
Tolerogenics offers the use of plain anionic PLGA nanospheres (size 300-500 nm) as a tolerance-promoting adjuvant in combination with established allergen-specific immunotherapy approaches.
The study of Eldridge et al. (1991, Infect. Immunity 59:2978-2996) provides first data suggesting a tolerogenic effect of plain PLGA particles. The published data show that antibody development upon subcutaneous injection of a mixture of SEB toxoid and plain PLGA particles is poor as compared to the other immunization procedures.
First substantial support for a tolerogenic effect of plain PLGA particles is provided by the study of Kim et al. (2002, Arthritis Rheum. 46:1109-1120). In this study oral tolerance induction in animals with collagen-induced arthritis (CIA) was investigated using PLGA nanoparticles (approx. 300 nm in size) containing entrapped collagen II. Here, plain PLGA particles were used as control and showed tolerogenic effects.
Solid support for a tolerogenic effect of plain PLGA particles is provided by the study of Jilek et al. (2004a). Using a murine phospholipase A2-iduced allergy model, Jilek et al. (2004, J. Allergy Clin. Immunol. 114:943-950) have demonstrated that plain PLGA microspheres (size range, 1-10 mm) can induce tolerance for as long as 6 months post-sensitization. The published data suggest a dual mechanism that does initially rely on a Th2 to Th1 immune deviation and then on IL-10-mediated immune suppression.