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Development of drug delivery system using albumin nanoparticles for sustained intraocular release of brimonidine
지속적 안구내 약물 방출을 위한 알부민 나노입자 기반 약물 전달 시스템 개발

DC Field Value Language
dc.contributor.advisor박기호-
dc.contributor.author김고은-
dc.date.accessioned2017-07-14T01:39:42Z-
dc.date.available2017-07-14T01:39:42Z-
dc.date.issued2017-02-
dc.identifier.other000000141495-
dc.identifier.urihttps://hdl.handle.net/10371/122217-
dc.description학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2017. 2. 박기호.-
dc.description.abstractPurpose: Eye drops are one of the most common types of glaucoma medication notwithstanding their limitations in terms of bioavailability and low compliance. Albumin-based nanoparticles have shown potential for effective and continuous drug release. Thus, we investigated the potential of human serum albumin nanoparticle (HSA-NP) as a tool for sustained delivery of neuroprotective agent in optic nerve crush (ONC) injury model.
Methods: Albumin nanoparticles loaded with brimonidine (HSA-BRM-NPs) were prepared by ethanol precipitation, including 0.18% brimonidine (BRM) and 3.5% human serum albumin (HSA) in HSA-BRM-NP solution. In vitro release profile of BRM was measured using Spectra/por dialysis membrane and assessed by high-performance liquid chromatography. We performed ONC and intravitreal injection in Sprague-Dawley rats, which were divided into Normal, balanced salt solution (BSS)-injected ONC, HSA-NP-injected ONC, BRM-injected ONC, and HSA-BRM-NP-injected ONC groups. The survival of RGC was compared at 5 and 14 days after procedures.
Results: The HSA-BRM-NP released 95% BRM in a sustained manner for 3 days, and the rest until 5 days. The percentages of RGC survival in the HSA-NP (52.6 ± 3.3%), BRM (58.0 ± 4.2%), and HSA-BRM-NP (63.5 ± 7.1%) groups relative to Normal (100%) were significantly higher than in the BSS group (29.2 ± 3.3%) 5 days after ONC (P < 0.001). At 5 days, no significant difference was found in the percentage of RGC survival between BRM and HSA-BRM-NP groups (P = 0.014). However, the HSA-BRM-NP (38.1 ± 3.6%) group showed significantly higher RGC density than the BRM (18.6 ± 3.9%, P = 0.006) group at 14 days.
Conclusions: Albumin nanoparticles showed sustained therapeutic effect with the combined neuroprotective agent. Our results suggest the potential of albumin nanoparticles as a promising tool for sustained intraocular drug release.
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dc.description.tableofcontents1. Introduction 1
2. Materials and Methods 3
2.1 Materials 3
2.2 Preparation of human serum albumin nanoparticles loaded with brimonidine 3
2.3 Characterization of human serum albumin nanoparticles loaded with brimonidine 4
2.4 Optic nerve crush injury model 5
2.5 Intravitreal injection of test agents 6
2.6 Evaluation of retinal ganglion cell survival 7
2.7 In vivo retinal distribution of human serum albumin nanoparticles loaded with brimonidine 8
2.8 Immunohistochemistry for amyloid-β 8
2.9 Cell viability assay for human serum albumin inhibition of amyloid-β aggregation 9
2.10 Statistical analysis 10
3. Results 11
3.1 Characterization of nanoparticles 11
3.2 In vivo retinal distribution of human serum albumin nanoparticles loaded with brimonidine 11
3.3 Sustained therapeutic effect of human serum albumin nanoparticles loaded with brimonidine on retinal ganglion cell survival 11
3.4 Neuroprotective mechanism of human serum albumin nanoparticles 12
4. Discussion 20
5. References 27
6. 국문초록 35
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dc.formatapplication/pdf-
dc.format.extent775314 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectHuman serum albumin-nanoparticle-
dc.subjectBrimonidine-
dc.subjectSustained drug release-
dc.subjectRetinal ganglion cell-
dc.subjectOptic nerve crush injury model-
dc.subject.ddc610-
dc.titleDevelopment of drug delivery system using albumin nanoparticles for sustained intraocular release of brimonidine-
dc.title.alternative지속적 안구내 약물 방출을 위한 알부민 나노입자 기반 약물 전달 시스템 개발-
dc.typeThesis-
dc.contributor.AlternativeAuthorKo Eun Kim-
dc.description.degreeDoctor-
dc.citation.pages37-
dc.contributor.affiliation의과대학 의학과-
dc.date.awarded2017-02-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Ph.D. / Sc.D._의학과)
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