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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

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Authors
김고은
Advisor
박기호
Major
의과대학 의학과
Issue Date
2017-02
Publisher
서울대학교 대학원
Keywords
Human serum albumin-nanoparticleBrimonidineSustained drug releaseRetinal ganglion cellOptic nerve crush injury model
Description
학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2017. 2. 박기호.
Abstract
Purpose: 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.
Language
English
URI
https://hdl.handle.net/10371/122217
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Ph.D. / Sc.D._의학과)
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