난용성 약물의 제어방출을 위한 열 변성 알부민-올레산 접합 나노입자의 제조

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dc.contributor.advisor이범진-
dc.contributor.author신민철-
dc.date.accessioned2019-04-01T16:40:56Z-
dc.date.available2019-04-01T16:40:56Z-
dc.date.issued2019--2-
dc.identifier.other28849-
dc.identifier.urihttps://dspace.ajou.ac.kr/handle/2018.oak/14974-
dc.description학위논문(석사)--아주대학교 일반대학원 :약학과,2019. 2-
dc.description.tableofcontents1. Introduction 1 2. Materials and Methods 8 2.1. Materials 8 2.2. Preparation of HSA-oleic acid conjugated nanoparticles 8 2.3. Optimization of AONs 11 2.4. Fourier transform infrared (FT-IR) 11 2.5. Preparation of CLT loaded AONs 12 2.5.1. The effect of heating temperature 13 2.5.2. The effect of heating time 13 2.6. Characterization of CLT loaded nanoparticles 16 2.6.1. Dynamic light scattering (DLS) 16 2.6.2. Field emission scanning electron microscopy (FE-SEM) 17 2.6.3. Circular dichroism spectropolarimeter (CD) 17 2.6.4. Determination of the drug loading contents (DL) and encapsulation efficiency (EE) 18 2.7. In vitro release profile 19 3. Results and discussions 20 3.1. Characterization and optimization of AONs 20 3.1.1. Physicochemical properties of AONs 20 3.1.2. Identification of HSA-oleic acid conjugates 24 3.2. Optimization of CLT loaded AONs 26 3.2.1. Effect of heating temperature 27 3.2.1.1. Circular dichroism spectropolarimeter (CD) 31 3.2.1.2. In vitro release profile 35 3.2.2. Effect of heating time 37 3.2.2.1. In vitro release profile 39 4. Conclusions 41 5. References 42 국문초록 47-
dc.language.isoeng-
dc.publisherThe Graduate School, Ajou University-
dc.rights아주대학교 논문은 저작권에 의해 보호받습니다.-
dc.title난용성 약물의 제어방출을 위한 열 변성 알부민-올레산 접합 나노입자의 제조-
dc.title.alternativeMincheol Shin-
dc.typeThesis-
dc.contributor.affiliation아주대학교 일반대학원-
dc.contributor.alternativeNameMincheol Shin-
dc.contributor.department일반대학원 약학과-
dc.date.awarded2019. 2-
dc.description.degreeMaster-
dc.identifier.localId905371-
dc.identifier.uciI804:41038-000000028849-
dc.identifier.urlhttp://dcoll.ajou.ac.kr:9080/dcollection/common/orgView/000000028849-
dc.description.alternativeAbstractThe purpose of this study was to investigate the effect of thermal denaturation on albumin nanoparticles (NPs) conjugated with fatty acid for the controlled release of poorly water-soluble drug. Albumin - oleic nanoparticle (AON) was prepared as follows. Sodium oleate was covalently conjugated to the backbone of human serum albumin (HSA) based on 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) reaction to form self-assembled fattigation-platform nanoparticles (NPs) using a simple nanoprecipitation method. Optimization of the stability of AONs was carried out using different concentrations of glutaraldehyde from which 1% concentration was selected. Cilostazol (CLT) was chosen as a model hydrophobic drug and loaded during the process of preparation to NPs by in process method. The formed AON was then dispersed in different heating condition for denaturation of albumin. Effect of mainly two factors, i.e., heating temperature and heating time, were evaluated for drug release from CLT-loaded AONs. Circular dichroism spectropolarimeter (CD) was used to investigate the structural change of human serum albumin after denaturation. Other physicochemical properties such as particle size and shape, CLT drug loading (%), loading efficiency (%), and release profile were also characterized. For in vitro release studies, thermally modified AON were injected into a dialysis bag containing 0.2 % (w/v) sodium lauryl sulfate (10 mL) in pH 7.4 buffer at 37°C using an incubation shaker at 100 rpm. The concentration of CLT was determined by RP-HPLC at 257 nm. CD spectra exhibited change in HSA secondary structure by heating denaturation. In addition, the degree of denaturation increased as heating intensity became higher. The sustained release effect was proportional to the degree of secondary structural modification of HSA. Moreover, the solubilizing effect of amphiphilic AONs was visible in all the samples. The thermal modification of amphiphilic AON could provide a versatile tool to modulate solubility and release rate of poorly water-soluble drugs.-
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