A drug delivery hydrogel system based on activin B for Parkinson's disease.
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.
Guangdong Provincial Key Laboratory of Proteomics and Key Laboratory of Transcriptomics and Proteomics of Ministry of Education of China, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Juan
J
Li
Department of Mechanical Engineering, Biochemistry and Medical Genetics, University of Manitoba, Manitoba Institute of Child Health, Winnipeg, MB, R3T 2N2, Canada.
Mohammadali
M
Darabi
Guangdong Provincial Key Laboratory of Proteomics and Key Laboratory of Transcriptomics and Proteomics of Ministry of Education of China, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Jingjing
J
Gu
Department of Mechanical Engineering, Biochemistry and Medical Genetics, University of Manitoba, Manitoba Institute of Child Health, Winnipeg, MB, R3T 2N2, Canada.
Junbin
J
Shi
Guangdong Provincial Key Laboratory of Proteomics and Key Laboratory of Transcriptomics and Proteomics of Ministry of Education of China, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Jinhua
J
Xue
Guangdong Provincial Key Laboratory of Proteomics and Key Laboratory of Transcriptomics and Proteomics of Ministry of Education of China, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Lu
L
Huang
Guangdong Provincial Key Laboratory of Proteomics and Key Laboratory of Transcriptomics and Proteomics of Ministry of Education of China, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Yutong
Y
Liu
Guangdong Provincial Key Laboratory of Proteomics and Key Laboratory of Transcriptomics and Proteomics of Ministry of Education of China, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Lei
L
Zhang
Elderly Health Services Research Center, Southern Medical University, Guangzhou, 510515, China.
N
N
Liu
Department of Textile Sciences, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada.
Wen
W
Zhong
Guangdong Provincial Key Laboratory of Proteomics and Key Laboratory of Transcriptomics and Proteomics of Ministry of Education of China, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: zlilyzh@126.com.
Lin
L
Zhang
Department of Mechanical Engineering, Biochemistry and Medical Genetics, University of Manitoba, Manitoba Institute of Child Health, Winnipeg, MB, R3T 2N2, Canada. Electronic address: Malcolm.xing@umanitoba.ca.
Malcolm
M
Xing
Guangdong Provincial Key Laboratory of Proteomics and Key Laboratory of Transcriptomics and Proteomics of Ministry of Education of China, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China; Elderly Health Services Research Center, Southern Medical University, Guangzhou, 510515, China. Electronic address: zlulu70@126.com.
Lu
L
Zhang
D028341:Activins / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D045744:Cell Line, Tumor; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D016503:Drug Delivery Systems; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage / Q000737:chemistry*; D007267:Injections; D008297:Male; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology; D012212:Rheology
D018696:Neuroprotective Agents; C044147:activin B; D028341:Activins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
Activin B; Biomaterials; Drug release; Parkinson's disease; Thermosensitive hydrogel