title: Toward immunosuppressive effects on liver transplantation in rat model: tacrolimus loaded poly(ethylene glycol)-poly(D,L-lactide) nanoparticle with longer survival time.
abstract: 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.
authors.affiliation: School of Pharmaceutical Science, Shandong University, Jinan 250012, China; Department of Pharmacy, Shandong Provincial Qian Foshan Hospital, Jinan 250014, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Science, Shandong University, Jinan 250012, China; Institute of Biopharmaceuticals of Shandong Province, Jinan 250101, China. Electronic address: sdfrdlpx@126.com.
authors.forename: Peixue
authors.initials: P
authors.lastname: Ling
authors.affiliation: Institute of Biopharmaceuticals of Shandong Province, Jinan 250101, China.
authors.forename: Tianmin
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D057809:HEK293 Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016031:Liver Transplantation; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D016559:Tacrolimus / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D007166:Immunosuppressive Agents; D011091:Polyesters; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols; D016559:Tacrolimus
keywords: Immunosuppressive; Liver transplantation; MPEG-PLA; Nanoparticle; Tacrolimus