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Deoxycholic Acid-Conjugated Polyethylenimine for Delivery of Heme Oxygenase-1 Gene in Rat Ischemic Stroke Model

Title
Deoxycholic Acid-Conjugated Polyethylenimine for Delivery of Heme Oxygenase-1 Gene in Rat Ischemic Stroke Model
Author
이민형
Keywords
conjugation; nonviral gene delivery; gene therapy; polymeric drug carrier; plasmid DNA
Issue Date
2017-08
Publisher
WILEY
Citation
JOURNAL OF PHARMACEUTICAL SCIENCES, v. 106, no. 12, page. 3524-3532
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. (C) 2017 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
URI
https://jpharmsci.org/article/S0022-3549(17)30555-5/fulltexthttp://repository.hanyang.ac.kr/handle/20.500.11754/115247
ISSN
0022-3549; 1520-6017
DOI
10.1016/j.xphs.2017.07.020
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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