Old Dog New Tricks: PLGA Microparticles as an Adjuvant for Insulin Peptide Fragment-Induced Immune Tolerance against Type 1 Diabetes

Abstract

Poly[lactic-co-(glycolic acid)] (PLGA) is arguably one of the most versatile synthetic copolymers used for biomedical applications. In vivo delivery of multiple substances including cells, pharmaceutical compounds and antigens has been achieved by using PLGA-based micro-/nanoparticles, although presently the exact biological impact of PLGA particles on the immune system remains controversial. Type 1 diabetes (T1D) is one subtype of diabetes characterised by the attack of immune cells against self insulin-producing pancreatic islet cells. Considering the autoimmune aetiology of T1D and the recent use of PLGA particles for eliciting desired immune responses in various aspects of immunotherapy, for the present study, a combination of Ins29-23 peptide (a known autoantigen of T1D) and PLGA microparticles was selected for T1D prevention assessment in non-obese diabetic (NOD) mice, a well-known animal model with spontaneous development of T1D. Thus, inoculation of PLGA microparticles+Ins29-23 completely prevented T1D development, significantly better than untreated controls and mice treated by either PLGA microparticles or Ins29-23 per se. Subsequent mechanistic investigation further revealed a facilitative role of PLGA microparticles on both central and peripheral immune tolerance induction. In summary, our data demonstrate an adjuvant potential of PLGA microparticles in tolerance induction and immune remodulation for effective prevention of autoimmune diseases such as T1D.