Novel nano-microspheres containing chitosan, hyaluronic acid, and chondroitin sulfate deliver growth and differentiation factor-5 plasmid for osteoarthritis gene therapy.

Zhu Chen; Shang Deng; De-chao Yuan; Kang Liu; Xiao-cong Xiang; Liang Cheng; Dong-qin Xiao; Li Deng; Gang Feng

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Novel nano-microspheres containing chitosan, hyaluronic acid, and chondroitin sulfate deliver growth and differentiation factor-5 plasmid for osteoarthritis gene therapy.

Author: Zhu CHEN ¹ ; Shang DENG ¹ ; De-Chao YUAN ¹ ; Kang LIU ¹ ; Xiao-Cong XIANG ¹ ; Liang CHENG ² ; Dong-Qin XIAO ¹ ; Li DENG ¹ ; Gang FENG ¹
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1. Institute of Tissue Engineering and Stem Cells, Nanchong Central Hospital, the Second Clinical Medical College of North Sichuan Medical College, Nanchong 637000, China.
2. Department of General Surgery, Chinese Medicine Hospital of Nanchong, Nanchong 637000, China.
Publication Type:Journal Article
Keywords: Osteoarthritis; Gene therapy; Chitosan; Hyaluronic acid; Chondroitin sulfate; Growth and differentiation factor-5 (GDF-5) plasmid
MeSH: Animals; Cell Differentiation; Cell Survival/drug effects*; Chitosan/chemistry*; Chondrocytes/cytology*; Chondroitin Sulfates/chemistry*; Drug Carriers; Extracellular Matrix/metabolism*; Genetic Therapy/methods*; Growth Differentiation Factor 5/genetics*; Hyaluronic Acid/chemistry*; Microspheres; Nanomedicine; Osteoarthritis/therapy*; Plasmids/metabolism*; Rabbits
From: Journal of Zhejiang University. Science. B 2018;19(12):910-923
CountryChina
Language:English
Abstract: OBJECTIVE:To construct a novel non-viral vector loaded with growth and differentiation factor-5 (GDF-5) plasmid using chitosan, hyaluronic acid, and chondroitin sulfate for osteoarthritis (OA) gene therapy.
METHODS:Nano-microspheres (NMPs) were prepared by mixing chitosan, hyaluronic acid, and chondroitin sulfate. GDF-5 plasmid was encapsulated in the NMPs through electrostatic adsorption. The basic characteristics of the NMPs were observed, and then they were co-cultured with chondrocytes to observe their effects on extracellular matrix (ECM) protein expression. Finally, NMPs loaded with GDF-5 were injected into the articular cavities of rabbits to observe their therapeutic effects on OA in vivo.
RESULTS:NMPs exhibited good physicochemical properties and low cytotoxicity. Their average diameter was (0.61±0.20) μm, and encapsulation efficiency was (38.19±0.36)%. According to Cell Counting Kit-8 (CCK-8) assay, relative cell viability was 75%-99% when the total weight of NMPs was less than 560 μg. Transfection efficiency was (62.0±2.1)% in a liposome group, and (60.0±1.8)% in the NMP group. There was no significant difference between the two groups (P>0.05). Immunohistochemical staining results suggested that NMPs can successfully transfect chondrocytes and stimulate ECM protein expression in vitro. Compared with the control groups, the NMP group significantly promoted the expression of chondrocyte ECM in vivo (P<0.05), as shown by analysis of the biochemical composition of chondrocyte ECM. When NMPs were injected into OA model rabbits, the expression of ECM proteins in chondrocytes was significantly promoted and the progression of OA was slowed down.
CONCLUSIONS:Based on these data, we think that these NMPs with excellent physicochemical and biological properties could be promising non-viral vectors for OA gene therapy.