The pro-inflammatory response of macrophages regulated by acid degradation products of poly(lactide-co-glycolide) nanoparticles

Poly(lactide-co-glycolide) (PLGA) shows great potentials in biomedical applications, in particular with the field of biodegradable implants and control release technologies. However, there are few systematic and detailed studies on the influence of PLGA degradation behavior on the immunogenicity. In this study, in order to develop a method for dynamically assessing the immunological response of PLGA throughout the implantation process, PLGA particles are fabricated using an o/w single-emulsion method. The physicochemical characterizations of the prepared PLGA particles during in vitro hydrolytic degradation are investigated. Then, a series of immunological effects triggered by PLGA by-products formed with degradation process are evaluated, including cell viability, apoptosis, polarization and inflammatory reaction. THP-1 human cell line is set as in vitro cell model. Our results show that PLGA degradation-induced acid environment decreases cell viability and increases cell apoptosis, which is a potential factor affecting cell function. In particular, the macrophages exhibit up-regulations in both M1 subtype related surface markers and pro-inflammatory cytokines with the degradation process of PLGA, which indicates the degradation products of PLGA can convert macrophages to the pro-inflammatory (M1) polarization state. All these findings provide the mechanism of PLGA-induced inflammation and lay the foundation for the design of next-generation PLGA-based biomaterials endowed with immunomodulatory functions.