Poly(Lactic-Co-Glycolic Acid) (PLGA) Nanoparticles Loaded with FK506 Inhibits Acute Heart Transplantation Rejection via Regulation of Monocyte Dendritic Cells Receptor

Abstract

FK506-loaded poly(lactic-co-glycolic acid)-nanoparticles (PLGA-NPs) (PLGA-FK506-NPs) have been indicated to exert better curative effect on rejection. Therefore, were herein studied mechanism underlying PLGA-FK506-NPs suppression of heart transplantation rejection. After construction of heterotopic heart transplant model in rats and preparation of composite NPs, the animals were administered with normal saline, FK506 and PLGA-FK506-NPs. With measurement of survival time for transplanted hearts and detection of NPs toxicity, rat tissue sample was collected for Hematoxylin and eosin (H&E) staining observation. T cell infiltration and contents of IL-12 and IL-23 in dendritic cell (DCs) were also detected. In the presence of FK506 or PLGA-FK506-NPs, cell viability did not change significantly (p > 0.05), indicating low toxicity of PLGA-FK506-NPs. Importantly, treatment with FK506 or PLGA-FK506-NPs alleviated CD3+ T cell infiltration and rejection, compared with control group. Of note was that, 40% of the rat hearts in the PLGA-FK506-NPs group had an Acute Rejection (AR) level of 1R, but only 20% in the FK506 group. PLGA-FK506-NPs group had a longer heart transplant survival time than both control and FK506 groups (p <0.001). Over time, FK506 concentration decreased in blood from the rats in the FK506 and PLGA-FK506-NPs groups, indicating that, FK506 was gradually metabolized. Additionally, PLGA-FK506-NPs and FK506 resulted in increased secretion of IL-12 and IL-23, with a higher level in the PLGA-FK506-NPs group. PLGA-FK506-NPs can effectively increase FK506 content in the body, prolonging survival time of heart transplant recipients, relieving AR, and improving secretion of related factors in the mono-DCs recipients.