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Apatinib in HSA-PEG inhibits VEGF-induced retinal vascular permeability and angiogenesis
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | Sang Gyu Park | - |
| dc.contributor.author | KHANH, NGUYEN HON | - |
| dc.date.accessioned | 2018-11-08T08:21:57Z | - |
| dc.date.available | 2018-11-08T08:21:57Z | - |
| dc.date.issued | 2015-08 | - |
| dc.identifier.other | 20426 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/13154 | - |
| dc.description | 학위논문(석사)--아주대학교 일반대학원 :약학,2015. 8 | - |
| dc.description.tableofcontents | TABLE OF CONTENTS ABSTRACT i LIST OF FIGURES vii ABBREVIATION viii 1. INTRODUCTION 1 2. MATERIALS AND METHODS 4 2.1. Reagents 4 2.2. Cell culture 4 2.3. Cell viability assay 4 2.4. In vitro angiogenesis assays 4 2.5. Endothelial permeability assay 5 2.6. Measurement of transendothelial electrical resistance 6 2.7. Mice 6 2.8. Retinal vascular permeability in vivo assay 7 2.9. STZ-induced diabetic animal model 7 2.10. Statistical analysis 8 3. RESULTS 9 3.1. HSA-PEG and HSA-PEG/Apatinib did not induce cellular toxicity in retinal endothelial cells 9 3.2. HSA-PEG/Apatinib inhibited proliferation, tube formation and wounding migration of HRMECs in vitro 11 3.3 Inhibitory effect of HSA-PEG/Apatinib in VEGF-mediated hyperpermeability in retinal endothelial cells 16 3.4. Decrease in TEER of HRMECs by VEGF stimulation was recovered by treatment with HSA-PEG/Apatinib 17 3.5. HSA-PEG/Apatinib attenuated VEGF-mediated vascular hyperpermeability in the mouse retina 18 3.6. Intravitreal injection of HSA-PEG/Apatinib inhibits retinal vascular leakage in STZ-induced diabetic mice 20 4. DISCUSSION 22 5. CONCLUSION 26 6. REFERENCES 27 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | Apatinib in HSA-PEG inhibits VEGF-induced retinal vascular permeability and angiogenesis | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.department | 일반대학원 약학 | - |
| dc.date.awarded | 2015. 8 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 705402 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000020426 | - |
| dc.subject.keyword | angiogenesis | - |
| dc.subject.keyword | permeability | - |
| dc.subject.keyword | VEGF | - |
| dc.subject.keyword | diabetic retinopathy | - |
| dc.description.alternativeAbstract | Objective: The vascular endothelial growth factor (VEGF) family plays a pivotal role in controlling pathologic vascular angiogenesis and permeability in important eye diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Developing new therapy in addition to the conventional treatment such as laser photocoagulation to suppress VEGF-induced excessive retinal vascular permeability has emerged as a major research focus. Methods and Results: In this study, we investigated the effect of HSA-PEG/Apatinib-a specific inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) using a murine model and human retinal microvascular endothelial cell line (HRMEC). Apatinib was efficiently loaded in HSA-PEG, a type of self-assembled nanostructures, which comprises of human serum albumin (HSA) and (poly)ethyleneglycol (PEG) to increase the solubility of water-insoluble drug, thus enhancing pharmacokinetics and bioavailability. To evaluate whether HSA-PEG/Apatinib could inhibit the VEGF-induced angiogenesis, the endothelial proliferation, tube formation and wounding migration were conducted. To assess vascular permeability, in vitro transendothelial resistance and paracellular permeability to dextran and in vivo leakage of intravenous FITC-labeled albumin and Evans blue dye into the retina were measured. Herein, we demonstrated that HSA-PEG/Apatinib significantly inhibited VEGF-induced angiogenesis and hyperpermeability in human retinal microvascular endothelial cells in vitro. In vivo, HSA-PEG/Apatinib significantly inhibited VEGF-mediated vascular leakage and diabetes-induced vascular breakdown in the retinal vessels. Conclusion: Taken together, our findings showed that HSA-PEG/Apatinib could be a potential therapeutic treatment of VEGF-mediated retinal vascular angiogenesis and hyperpermeability in variable ocular diseases. | - |
| dc.title.subtitle | Apatinib in HSA-PEG inhibits VEGF-induced retinal vascular permeability and angiogenesis | - |
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- Graduate School of Ajou University > Department of Pharmacy > 3. Theses(Master)
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