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Injectable gelatin-peg hydrogels for long-term delivery of dexamethasone or avastin to treat choroidal neovascularization
- Alternative Title
- Joo Young Son
- Author(s)
- 손주영
- Alternative Author(s)
- Joo Young Son
- Advisor
- 박기동
- Department
- 일반대학원 분자과학기술학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2020-02
- Language
- eng
- Alternative Abstract
- Abstract Injectable hydrogel systems have received much attention due to their versatile and tunable characteristics based on a minimal invasive technique. In a free flow state, hydrogel precursor solutions can fill up a tissue defect or target site while containing bioactive molecules, and then act as a localized therapeutic depot after physical or chemical cross-linking. A horseradish peroxidase (HRP)-catalyzed cross-linking reaction has recently received much attention as a promising approach to developing in situ forming hydrogels. For the reaction, HRP and hydrogen peroxide (H2O2) are both considered as essential prerequisites for controlling the degree and rate of cross-linking. Choroidal neovascularization (CNV) resulted by various retina and posterior segment disease particularly age‐related macular degeneration is among the main causes of blindness worldwide and in light of ongoing population ageing its prevalence is increasing specially in developed countries. As a major health concern, these ocular diseases have detrimental effects on patients’ quality of life and society economy. Considering the key role of vascular endothelium growth factor (VEGF) in the pathogenesis of CNV, Although the pathophysiology of macular edema is not yet fully understood, VEGF has been recognized as a major contributor. VEGF inhibitors have changed the paradigm of therapy and have become the standard of care during the last decade. Dexamethasone has potentially many more pathogenic targets and thus much more potential to address a therapeutic response on chronic/recalcitrant, longstanding, or severe macular edema. Avastin is a full‐length humanized antibody against all isoforms of VEGF. Avastin is widely used intravitreally in the treatment of CNV as an off‐labeled drug. Dexamethasone and Avastin have demonstrated promising effect on treatment of the disease, repetitive intravitreal injection is required due to short half‐life of the drug in vitreous. The frequency of intravitreal injection would be a leading cause in reducing patient compliance besides deleterious adverse effects including retinal detachment, subconjunctival hemorrhage and endophthalmitis. Hence, developing extended release drug delivery systems seems to be necessary to decrease the number of administrations. The main objective of this dissertation is to develop and evaluate injectable gelatin hydrogels for long term drug delivery of dexamethasone or avastin to treat choroidal neovascularization. The first work of the thesis was to prepare and characterize an injectable gelatin hydrogel via HRP catalyzed cross-linking. The gelatin hydrogels were prepared from a gelatin solution above 3 wt% in the presence of their mechanical properties such as gelation time, elastic modulus and degradation time were evaluated at different HRP, H2O2 concentration. Drug release behaviors from hydrogel were evaluated HPLC (dexamethasone) and ELISA (avastin). Through circular dichroism analysis, the structural stability of released avastin from the gelatin hydrogel was confirmed. In the cell study, the drug loaded hydrogels showed no apparent cytotoxicity. We intravitreal injected the drug loaded hydrogels into the eyes of SD rats and rabbits. The results of in vivo study demonstrated successful injection of the drug loaded hydrogel at the injected site and excellent therapeutic efficacy and pharmacokinetics.
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- Appears in Collections:
- Graduate School of Ajou University > Department of Molecular Science and Technology > 4. Theses(Ph.D)
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