2. Academic Validation
  3. Delivery of FK506-loaded PLGA nanoparticles prolongs cardiac allograft survival

Delivery of FK506-loaded PLGA nanoparticles prolongs cardiac allograft survival

  • Int J Pharm. 2020 Feb 15;575:118951. doi: 10.1016/j.ijpharm.2019.118951.
Cheng Deng 1,  Yihan Chen 1,  Li Zhang 1,  Ya Wu 1,  Huiling Li 1,  Yu Wu 1,  Bin Wang 1,  Zhenxing Sun 1,  Yuman Li 1,  Qing Lv 1,  Yali Yang 1,  Jing Wang 1,  Qiaofeng Jin 2,  Mingxing Xie 3
Affiliations

Affiliations

  • 1 Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, China.
  • 2 Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, China. Electronic address: jin_qf@hust.edu.cn.
  • 3 Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, China. Electronic address: xiemx@hust.edu.cn.
PMID: 31843550 DOI: 10.1016/j.ijpharm.2019.118951
Abstract

In this study, FK506-loaded poly(lactide-co-glycolide) nanoparticles (PLGA-FK506-NPs) were developed using an O/W emulsion solvent evaporation method. The PLGA-FK506-NPs were observed to be monodispersed and spherical by transmission and scanning electron microscopy. The mean size and zeta potential measured by dynamic LIGHT scattering were 110 ± 1.3 nm and -20.56 ± 3.65 mV, respectively. The FK506 entrapment and loading efficiency were 94.46 ± 1.88% and 5.38 ± 0.24%, respectively. Moreover, a pharmacokinetics study revealed that the PLGA-FK506-NPs behaved significantly different than free FK506 by exhibiting a higher area under curve (1.69-fold), higher mean residence time (1.29-fold), slower clearance and longer elimination half-life. Notably, the concentrations of FK506 in the spleen and mesenteric lymph nodes of the PLGA-FK506-NP group were 3.1-fold and 2.9-fold higher than those of the free FK506 group. Furthermore, the immunosuppressive efficacy was evaluated in a rat heterotopic heart transplantation model, and the results showed that PLGA-FK506-NP treatment could successfully alleviate acute rejection and prolong allograft survival compared with the free FK506 treatment (mean survival time, 17.1 ± 2.0 versus 13.3 ± 1.7 days). In conclusion, PLGA-FK506-NPs are a promising formulation for spleen and lymph node delivery and have potential use in the treatment of cardiac allograft acute rejection.

Keywords

Acute rejection; FK506; Heart transplantation; Lymph node; Nanoparticle; PLGA.

Figures
Products