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뇌졸중 유전자치료를 위한 덱사메타손이 봉입된 RV 펩타이드 마이셀의 개발

Title
뇌졸중 유전자치료를 위한 덱사메타손이 봉입된 RV 펩타이드 마이셀의 개발
Other Titles
Development of dexamethasone loaded micelles for stroke gene therapy
Author
이지영
Advisor(s)
이민형
Issue Date
2011-02
Publisher
한양대학교
Degree
Master
Abstract
R3V6 peptides which are composed of 3 arginines and 6 valines, formed self assembled micelles in aqueous phase with hydrophobic cores of valines and cationic surface of arginines. Dye quenching assays showed that hydrophobic fluorescent dye 5-dodecanoylaminofluorescein(DAF) interacted with and was loaded into the hydrophobic core of the micelles. In this study, dexamethasone was loaded as hydrophobic anti-inflammatory drug into the core of the peptide micelles. Dexamethasone loaded R3V6 peptides (R3V6-Dexamethasone) were also evaluated as a gene carrier as well as a drug carrier. In vitro transfection assay showed that R3V6-Dexamethasone had higher gene delivery efficiency than R3V6 peptides. It may be that hydrophobic dexamethasone stabilizes the micelle structure of R3V6 peptide by forming strong hydrophobic cores. Furthermore, R3V6-Dexamethasone reduced inflammatory cytokine level more efficiently than dexamethasone in lipopolysaccharides (LPS)-induced Raw264.7 cells.R3V6-Dexamethasone did not show any cytotoxicity in human embryonic kidney 293 (HEK 293) cells. Focal brain ischemia model was produced by middle cerebral artery occlusion (MCAO). A heme oxygenase-1 (HO-1) expression plasmid, pEpo-SV-HO-1, was complexed with R3V6-Dexamethasone. pEpo-SV-HO-1/R3V6-Dexamethasone complex was injected into the brain 1 hr prior to MCAO. Twenty four hours after ischemia-reperfusion, brain infarct size was measured by TTC staining. The results showed that the infarct size was reduced by the delivery of pEpo-SV-HO-1/R3V6-Dexamethasone complex. The results suggest that R3V6-Dexamethasone is useful in HO-1 gene delivery and stroke gene therapy with high transfection efficiency, low toxicity and anti-inflammatory effect.
URI
https://repository.hanyang.ac.kr/handle/20.500.11754/140013http://hanyang.dcollection.net/common/orgView/200000416171
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIOENGINEERING(생명공학과) > Theses (Master)
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