Deoxycholic Acid-Conjugated Polyethylenimine for Delivery of Heme Oxygenase-1 Gene in Rat Ischemic Stroke Model
- Authors
- Oh, Jungju; Lee, Min Sang; Jeong, Ji Hoon; Lee, Minhyung
- Issue Date
- Dec-2017
- Publisher
- WILEY
- Keywords
- conjugation; nonviral gene delivery; gene therapy; polymeric drug carrier; plasmid DNA
- Citation
- JOURNAL OF PHARMACEUTICAL SCIENCES, v.106, no.12, pp.3524 - 3532
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF PHARMACEUTICAL SCIENCES
- Volume
- 106
- Number
- 12
- Start Page
- 3524
- End Page
- 3532
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/5330
- DOI
- 10.1016/j.xphs.2017.07.020
- ISSN
- 0022-3549
- Abstract
- An efficient gene carrier to the brain is required for successful gene therapy of ischemic stroke. In this study, deoxycholic acid-conjugated polyethylenimine (DA-PEI) was synthesized and evaluated as a heme oxygenase-1 (HO-1) gene carrier for ischemic stroke gene therapy. Gel retardation assay and heparin competition assay showed that DA-PEI formed a stable complex with plasmid DNA. In vitro transfection assays with the luciferase gene showed that DA-PEI had higher transfection efficiency than polyethylenimine (25 kDa, PEI25k) and lipofectamine in Neuro2A cells. Furthermore, DA-PEI had less toxicity than lipofectamine. To evaluate the therapeutic effects of the pb-HO-1/DA-PEI complex, the complex was injected locally in the brain of the transient middle cerebral artery occlusion animal model. In in vivo studies, DA-PEI was more effective than PEI25k in delivering pb-HO-1 to the ischemic brain and achieved higher HO-1 expression. As a result, the pb-HO-1/DA-PEI complexes more effectively reduced infarct volume and the number of apoptotic cells compared with the pb-HO-1/PEI25k complex. The results suggest that DA-PEI will be useful for HO-1 gene therapy of ischemic stroke.
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