Toward immunosuppressive effects on liver transplantation in rat model: Tacrolimus loaded poly(ethylene glycol)-poly(d,l-lactide) nanoparticle with longer survival time

In this study, tacrolimus (FK506) was encapsulated into a biodegradable poly(ethylene glycol)-poly(d,l-lactide) (MPEG-PLA) block copolymer using a double emulsion-solvent evaporation technique. Drug loading (DL) and encapsulation efficiency (EE) can be changed by varying the mass ratio of FK506/MPEG-PLA. Furthermore, transmission electron microscope (TEM) and Malvern Zetasizer were used to investigate the properties of FK506/MPEG-PLA nanoparticles (DL = 9.5%), which were monodisperse (PDI = 0.100 ± 0.023) with a mean particle size of 90.5 ± 1.5 nm. Compared with FK506 capsule, in vitro release profile showed that FK506/MPEG-PLA nanoparticles exhibited sustained release. Meanwhile, the higher concentration and longer retention time in plasma were also confirmed in vivo. We further preliminarily evaluated immunosuppressive effect on liver transplantation in rat model. The survival time of the rat administrated FK506/MPEG-PLA nanoparticles was obviously prolonged than that of the control group administrated FK506 capsule.

Graphical abstractIn this study, tacrolimus (FK506) was encapsulated into a biodegradable poly(ethylene glycol)-poly(d,l-lactide) (MPEG-PLA) block copolymer using a double emulsion-solvent evaporation technique. Compared with FK506 capsule, in vitro release profile showed that FK506/MPEG-PLA nanoparticles exhibited sustained release. Meanwhile, the higher concentration and longer retention time in plasma were also confirmed in vivo. The survival time of the rat administrated FK506/MPEG-PLA nanoparticles was obviously prolonged than that of the control group administrated FK506 capsule.Figure optionsDownload full-size imageDownload high-quality image (204 K)Download as PowerPoint slide