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Control of colloidal stability and bioavailability of lipid nanoparticles for oral delivery of food bioactives : 식품수준 생리활성물질의 경구 운반을 위한 지질나노입자의 콜로이드 안정성과 생체이용률 조절
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 최영진 | - |
dc.contributor.author | 반충진 | - |
dc.date.accessioned | 2017-07-13T08:25:09Z | - |
dc.date.available | 2018-10-25 | - |
dc.date.issued | 2016-08 | - |
dc.identifier.other | 000000137029 | - |
dc.identifier.uri | https://hdl.handle.net/10371/119529 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 농생명공학부, 2016. 8. 최영진. | - |
dc.description.abstract | Lipid carrier system capable of the controlled release for encapsulated bioactive materials has attracted an interest for the bioavailability increase and the targeted delivery of the bioactives in many industrial fields (foods, cosmetics, and pharmaceutics) for a long time. However, there was still no system as a perfect solution having both efficient functionality and economic feasibility. Lipid nanoparticle (LNP) system, including solid lipid nanoparticle and nanostructured lipid carrier, was invented as a novel strategy for substitution of conventional lipid carrier systems such as emulsion and liposome, with a little modification (the use of solid lipids) from the emulsion. LNPs have various merits for using physiological lipids, protecting from the outside stress, enhancing the oral bioavailability, modulating the release profile of core materials, and enabling the bulk production. Accordingly, despite many efforts of food scientists for applying LNPs to foods, it was not adopted in foods yet due to unsolved problems in terms of colloidal or storage stability. In this research, the LNP production process was optimized to enhance the stability, and flavonoid-loaded LNPs were developed to improve the bioaccessibility of the flavonoids based on the optimum process, then the uptake pattern of LNP-incorporated curcumins into the blood was controlled on the basis of modulating the lipid-water interfacial property. In detail, 6 min postsonication during the cooling process after the size reduction step of melted lipid droplets can diffuse self-assembled/solo emulsifiers onto the LNP surface, and the addition of 30 wt % oil into the solid lipid phase ameliorated the LNP colloidal stability resulting from the
crystallinity reduction of solid lipid matrix. Additionally, under the simulated in vitro gastrointestinal tract (GIT), bioaccessibility values of quercetin, naringenin, and hesperetin encapsulated in LNPs prepared using 3.5 wt % fully hydrogen canola oil, 1.5 wt % squalene, 1.083 wt % soybean lecithin, and 0.583 wt % Tween 20 were increased 11.71-, 5.03-, 4.76-fold than those of the native-formed flavonoids, respectively. Lastly, because the mimicked GIT hydrolysis of LNPs covered with various PEGylated emulsifiers was controlled by the LNP designs in aspects of the PEG length, the emulsifier concentration, and the lipid type, the plasma residence of curcumin encapsulated in the PEGylated LNPs would be successfully extended or shortened as the designs under the in vivo rat model for oral administration. In summary, these results suggest that LNP systems developed in this study can satisfy enough an expectation of manufacturers and customers as a food-grade lipid delivery system. In conclusion, this study could serve as a basis for further research that aims to develop delivery systems for foods and pharmaceutics. | - |
dc.description.tableofcontents | Chapter I. Literature Review: Lipid Nanoparticles (LNPs) as a Delivery Carrier for Orally Ingested Food Bioactives 1
I-1. Introduction 2 I-2. General Features of Lipid Nanoparticles 5 I-2-1. Ingredients 5 I-2-2. Production Methods 7 I-2-3. Sterilization and Secondary Processes after the Production 12 I-2-4. General Characteristics 15 I-2-5. Applications and Administration Routes 25 I-3. Consideration for Applying Lipid Nanoparticles to Food Industry 28 I-3-1. Regulation for Using Ingredients 28 I-3-2. Colloidal Stability in Food System 31 I-3-3. Delivery Target of Bioactive Materials among Digestive System 32 I-3-4. Choice of the Production Methods 34 I-3-5. Storage Stability 35 I-3-6. Economic Feasibility 37 I-4. Summary and Perspectives 38 I-5. References 40 Chapter II. Enhancing the Stability of Lipid Nanoparticle Systems by Sonication during the Cooling Step and Controlling the Liquid Oil Content 60 II-1. Introduction 61 II-2. Materials and Methods 64 II-2-1. Chemicals 64 II-2-2. Lipid Nanoparticle Preparation 65 II-2-3. Microscopic Observation 66 II-2-4. Determination of Rheological Properties 67 II-2-5. Differential Scanning Calorimetry (DSC) Measurement 68 II-2-6. Powder X-ray Diffraction (XRD) Analysis 69 II-2-7. Measurement of Lipid Nanoparticle Size 70 II-2-8. Quantification of Stable Lipid Nanoparticles 71 II-2-9. Determination of Tween 20 Surface Load 72 II-2-10. Statistical Analysis 74 II-3. Results and Discussion 75 II-3-1. Lipid Nanoparticle Preparation 75 II-3-2. Visual Stability of Lipid Nanoparticles 79 II-3-3. Morphological Characteristics of Lipid Nanoparticles and Gelation Phenomenon 84 II-3-4. Rheological Properties of Lipid Nanoparticles 92 II-3-5. Thermal Properties of Bulk Lipids and Lipid Nanoparticles 94 II-3-6. Proposed Mechanisms of the Increased Stability of Lipid Nanoparticles Due to Additional Sonication and Liquid Canola Oil in the Oil Phase 101 II-4. References 108 Chapter III. Improving Flavonoid Bioaccessibility using an Edible Oil-Based Lipid Nanoparticle for Oral Delivery 114 III-1. Introduction 115 III-2. Materials and Methods 119 III-2-1. Chemicals 119 III-2-2. Lipid Nanoparticle Production 120 III-2-3. Quantification of Nonaggregated Lipid Nanoparticles (Yield) 122 III-2-4. Measurements of Lipid Nanoparticle Size and ζ Potential 123 III-2-5. Entrapment Efficiency of the Flavonoid-Loaded Lipid Nanoparticles 124 III-2-6. Determining the in Vitro Digestion Patterns of the Lipid Nanoparticles 125 III-2-7. Statistical Analysis 129 III-3. Results and Discussion 130 III-3-1. Stability of the Blank Lipid Nanoparticles 130 III-3-2. Characteristics of Lipid Nanoparticles 134 III-3-3. In Vitro Digestion of Lipid Nanoparticles 137 III-4. References 146 III-5. Appendix: Optimization Blank Lipid Nanoparticle Formula Using Response Surface Methodology 152 III-5-1. Determining Crystallinity of the Lipid Nanoparticles 152 III-5-2. Determining the Optimum Formula for Blank Lipid Nanoparticles 153 III-5-3. Optimization of the Blank Lipid Nanoparticle Formula 156 III-5-4. References 162 Chapter IV. Sustained Release of Curcumin Encapsulated in PEGylated Lipid Nanoparticle upon Oral Administration 163 IV-1. Introduction 164 IV-2. Materials and Methods 167 IV-2-1. Chemicals 167 IV-2-2. Lipid Nanoparticle and Emulsion Fabrication 168 IV-2-3. Quantification of Nonaggregated Lipid Nanoparticles (yield %) 169 IV-2-4. Measuring the Size and ζ Potential of Lipid Nanoparticles and Emulsion 170 IV-2-5. Determination of Emulsifier Surface Load 171 IV-2-6. Entrapment Efficiency of the Curcumin-loaded Lipid Nanoparticles and Emulsion 173 IV-2-7. Colloidal Stability of Lipid Nanoparticles and Emulsion in High Salt and Acidic Conditions 174 IV-2-8. Determining the in Vitro Digestion Patterns of the Lipid Nanoparticles and Emulsion 175 IV-2-9. Pharmacokinetic Study 180 IV-2-10. Data Analysis 182 IV-3. Results and Discussion 183 IV-3-1. Characteristics of Lipid Nanoparticles 183 IV-3-2. Effects of Incubation Condition on Colloidal Stability of the Curcumin-loaded Lipid Nanoparticles 191 IV-3-3. In Vitro Digestion and Absorption of the Curcumin-loaded Lipid Nanoparticles 193 IV-4. References 208 IV-5. Appendix: Controlling the Digestibility of Lipid Nanoparticles Stabilized by PEGylated Emulsifiers 214 IV-5-1. Introduction 214 IV-5-2. Materials and Methods 217 IV-5-3. Results and Discussion 218 IV-5-4. Reference 244 국문 초록 249 | - |
dc.format | application/pdf | - |
dc.format.extent | 5059380 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | lipid nanoparticle (LNP) | - |
dc.subject | bioactive material | - |
dc.subject | colloidal stability | - |
dc.subject | bioavailability | - |
dc.subject | controlled release | - |
dc.subject.ddc | 630 | - |
dc.title | Control of colloidal stability and bioavailability of lipid nanoparticles for oral delivery of food bioactives | - |
dc.title.alternative | 식품수준 생리활성물질의 경구 운반을 위한 지질나노입자의 콜로이드 안정성과 생체이용률 조절 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Choongjin Ban | - |
dc.description.degree | Doctor | - |
dc.citation.pages | XVI, 250 | - |
dc.contributor.affiliation | 농업생명과학대학 농생명공학부 | - |
dc.date.awarded | 2016-08 | - |
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