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

Abstract

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.

Synergistic effects of arginine–glycine–aspartic acid and phosphatidylserine on the surface immunomodulation and osseointegration of titanium implants

“…37,38 For example, macrophages exhibit a proinflammatory response to the PLGA degradation products. 39 However, in this study, BMDM cultured on PLGAcoated Ti surfaces exhibited less proinflammatory responses compared with those on uncoated Ti surfaces (Fig. 2D-F).…”

In Vivo Safety and Efficacy of Chalcone-Loaded Microparticles with Modified Polymeric Matrix against Cutaneous Leishmaniasis

“…The drug-release kinetics at the injection site indicated that both CH8/PDE and CH8/PVDE MPs presented a biphasic curve, as expected for PLGA MPs [ 34 ], with an initial burst release in the first 24 h followed by a slower release up to 60 days. CH8/PVDE showed a faster release profile than CH8/PLGA, compatible with other studies demonstrating accelerated drug release from nanoparticles and other MPs when PLGA is blended with PVP [ 35 , 36 ].…”

Microsphere–Gel Composite System with Mesenchymal Stem Cell Recruitment, Antibacterial, and Immunomodulatory Properties Promote Bone Regeneration via Sequential Release of LL37 and W9 Peptides

“…The expression levels of iNOS and CD206 returned to a relatively low and balanced state, which may indicate that subsequent tissue repair and reconstruction will be carried out in a relatively stable microenvironment. It is worth noting that the expression of iNOS in the LL37-W9/PLGA-SIS group was the highest at 3 months, which may be due to the acidic residual degradation products of PLGA microspheres . The microspheres were initially encapsulated by SIS gel and did not cause changes in the pH value of the surrounding environment or the inflammatory response.…”

“…It is worth noting that the expression of iNOS in the LL37-W9/PLGA-SIS group was the highest at 3 months, which may be due to the acidic residual degradation products of PLGA microspheres. 55 The microspheres were initially encapsulated by SIS gel and did not cause changes in the pH value of the surrounding environment or the inflammatory response. The degradation time of PLGA microspheres was longer than that of the SIS gel, which may cause the up-regulated expression of iNOS in a limited range, but this did not cause a severe inflammatory response or impair the final osteogenic effect.…”