전단응력 감수성 알부민-지방산 나노입자의 설계 및 평가
Design and characterization of shear-sensitive fattigation-platform albumin nanoparticles
- 주제(키워드) Shear sensitive , fattigation , biomimetic fluidic system , nanoparticles
- 발행기관 아주대학교 일반대학원
- 지도교수 이범진
- 발행년도 2019
- 학위수여년월 2019. 2
- 학위명 석사
- 학과 및 전공 일반대학원 약학과
- 실제URI http://www.dcollection.net/handler/ajou/000000028847
- 본문언어 한국어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Abstract The objective of this study was to design shear-sensitive fattigation-platform albumin nanoparticles to release the cargo at a high shear stress sites. Sodium docosahexaenoic acid (DHA) was chosen as a fatty acid of fattigation-platform. Using 1-Ethyl-3-(3-aminopropyldimethyl) carbodiimide (EDC), the sodium DHA was conjugated with human serum albumin (HSA) via carbodiimide reaction. The different types of HSA-DHA nanoparticles were prepared via desolvation method using fattigation-platform for design shear-sensitive nanoparticles. The sodium DHA fatty acid which had a long carbon chain (C22) was selected to prepare to loose structure of fattigation nanoparticles and successfully conjugated with HSA. To make more shear-sensitive nanoparticles, HSA-DHA nanoparticles were prepared by adding polymer, polyethylenimine (PEI), which can weakly electrostatic interact with albumin. The physicochemical properties of HSA-DHA nanoparticles were identified using ATR FTIR, DLS, SEM. Drug loading capacity of these nanoparticles showed high drug loading content and encapsulation efficiency. Biomimetic microfluidic system (BMS) was established to evaluate the shear-sensitive response of the nanoparticles. The shear-sensitivity of HSA-DHA nanoparticles were evaluated using UV-vis turbidity to detect disintegration of nanoparticles and shear induced drug release. The HSA-DHA with PEI nanoparticles had great shear sensitivity compared to other HSA-DHA nanoparticles at a high shear stress. In our findings, the shear-sensitive fattigation-platform nanoparticles could be designed to release the cargo at a specific shear stress site such as stenosis and thrombosis in blood vessels.
more목차
1. Introduction 1
2. Materials and Methods 6
2.1. Materials 6
2.2. Preparation of HSA-DHA conjugated nanoparticles 7
2.2.1. Preparation of HSA-DHA nanoparticles 7
2.2.2. Preparation of HSA-DHA with polymer nanoparticles 9
2.2.3. Preparation of CLT-loaded HSA-DHA based nanoparticles 10
2.3. Characterization of HSA-DHA nanoparticles 12
2.3.1. Dynamic light scattering (DLS) 12
2.3.2. Field emission scanning electron microscope (FE-SEM) 12
2.3.3. Fourier transform infrared spectroscopy (FT-IR) 13
2.3.4. Determination of drug loading (DL) and encapsulation efficiency (EE) 13
2.4. Biomimetic microfluidic system experiment (BMS) 15
2.4.1. BMS Design for shear stress 15
2.4.2. Shear stress calculation for μ-slide chamber 17
2.5. Determination and evaluation of shear sensitive nanoparticles 20
2.5.1. Turbidity measurement 20
2.5.2. Shear-induced drug release 21
3. Results and discussions 22
3.1. Characterization of HSA-DHA nanoparticles 22
3.1.1. Identification of HSA-DHA nanoparticles 22
3.1.2. Physicochemical properties of the HSA-DHA nanoparticles 26
3.1.3. FE-SEM of HSA-DHA nanoparticles 28
3.1.4. Determination of drug loading (DL) and encapsulation efficiency (EE) 30
3.2. Evaluation of shear-sensitive HSA-DHA nanoparticles 32
3.3 Shear-induced drug release 37
4. Conclusions 39
5. References 40
국문초록 43
