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

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농업생명과학대학 농생명공학부
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서울대학교 대학원
lipid nanoparticle (LNP)bioactive materialcolloidal stabilitybioavailabilitycontrolled release
학위논문 (박사)-- 서울대학교 대학원 : 농생명공학부, 2016. 8. 최영진.
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.
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College of Agriculture and Life Sciences (농업생명과학대학)Dept. of Agricultural Biotechnology (농생명공학부)Theses (Ph.D. / Sc.D._농생명공학부)
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