A drug delivery hydrogel system based on activin B for Parkinson's disease

Juan Li, Mohammadali Darabi, Jingjing Gu, Junbin Shi, Jinhua Xue, Lu Huang, Yutong Liu, Lei Zhang, N. Liu, Wen Zhong, Lin Zhang, Malcolm Xing, Lu Zhang

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Activins are members of the superfamily of transforming growth factors and have many potential neuroprotective effects. Herein, at the first place, we verified activin B's neuroprotective role in a PD model, and revealed that activin B's fast release has limited function in the PD therapy. To this end, we developed a multi-functional crosslinker based thermosensitive injectable hydrogels to deliver activin B, and stereotactically injected the activin B-loaded hydrogel into the striatum of a mouse model of PD. The histological evaluation showed that activin B can be detected even 5 weeks post-surgery in PD mice implanted with activin B-loaded hydrogels, and activin B-loaded hydrogels can significantly increase the density of tyrosine hydroxylase positive (TH+) nerve fibers and reduce inflammatory responses. The behavioral evaluation demonstrated that activin B-loaded hydrogels significantly improved the performance of the mice in the PD model. Meanwhile, we found that hydrogels can slightly induce the activation of microglia cells and astrocytes, while cannot induce apoptosis in the striatum. Overall, our data demonstrated that the developed activin B-loaded hydrogels provide sustained release of activin B for over 5 weeks and contribute to substantial cellular protection and behavioral improvement, suggesting their potential as a therapeutic strategy for PD.

Original languageEnglish
Pages (from-to)72-86
Number of pages15
JournalBiomaterials
Volume102
DOIs
StatePublished - 1 Sep 2016
Externally publishedYes

Keywords

  • Activin B
  • Biomaterials
  • Drug release
  • Parkinson's disease
  • Thermosensitive hydrogel

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