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Chitosan-coated Lipid-Polymer Hybrid Nanoparticles for Oral Delivery of Nadroparin
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 진효언 | - |
| dc.contributor.author | 조희원 | - |
| dc.date.accessioned | 2022-11-29T02:32:28Z | - |
| dc.date.available | 2022-11-29T02:32:28Z | - |
| dc.date.issued | 2021-02 | - |
| dc.identifier.other | 30672 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/20009 | - |
| dc.description | 학위논문(석사)--아주대학교 일반대학원 :약학과,2021. 2 | - |
| dc.description.abstract | 경구 제형은 환자의 복약 순응도를 높일 수 있을 뿐 아니라 질병 관리에 장점이 있기 때문에 약물 전달에 선호되는 경로다. 그런데 저분자량 헤파린, 나드로파린은 분자의 크기가 크고 용해도가 높으며 장벽의 투과도가 좋지 않은 특성 때문에 현재까지 주사 투여로만 환자에게 사용되어왔다. 따라서, 본 연구에서는 나드로파린의 경구 전달을 위해 키토산 코팅 리피드 폴리머 하이브리드 나노입자를 제조하였다. 하이드로겔 중심부는 친수성 의약품의 캡슐화 양에 한계가 있는 리피드 나노입자의 성질에 대한 대안으로 사용되었다. 변형된 W/O/W 더블 에멀전 방법은 입자의 특성과 약물의 활성도를 적절하게 유지시킬 수 있는 적절한 제조 방법이었다. 키토산 코팅된 나노입자는 친수성 중심부와 리피드 껍질로 구성되었고, 물리적 흡착 및 표면에서의 상호 작용으로 키토산이 코팅되었다. 최적화된 제형의 물리화학적 특성은 입자 크기, 제타 전위, 그리고 캡슐화 효율을 측정하여 평가되었다. 위 조건에서의 안정성, 키토산 코팅된 나노입자의 형태학, 시험관내 약물 방출 등이 조사되었다. 키토산 코팅으로 최적화된 제형의 안정성은 입자 크기와 제타 전위 모두에서 값이 개선되었다. 키토산 코팅은 위 조건에서 나노 입자의 웅집을 줄여 안정성을 높일 수 있었다. 키토산 코팅된 나노입자의 방출률은 74.24%로 72시간 내 코팅되지 않은 나노입자 (81.45%)와 비교했을 때 약간 지연된 방출을 보였다. 키토산 코팅된 나노입자는 경구 전달을 위한 약물 전달 시스템으로서 유망한 접근방식이 될 수 있다. | - |
| dc.description.tableofcontents | 1. Introduction 1 2. Materials and Methods 6 2.1. Material 6 2.2. Preparation of lipid-polymer hybrid nanoparticles (LPNs) and chitosan-coated LPNs (C-LPNs) 6 2.3. Particle size and zeta potential studies 7 2.4. Encapsulation efficiency (EE%) 7 2.5. Stability test in simulated gastric condition 8 2.6. Transmission electron microscopy (TEM) 8 2.7. Lyophilization of nanoparticles 8 2.8. Differential scanning calorimetry (DSC) 9 2.9. Fourier transform infrared (FT-IR) 9 2.10. In vitro drug release study 9 2.11. Statistical analysis 10 3. Results and Discussion 11 3.1. Preparation and characterization of LPNs 11 3.2. Preparation and characterization of C-LPNs 15 3.3. Stability of nanoparticles in simulated gastric condition 18 3.4. Transmission electron microscopy (TEM) 20 3.5. Differential scanning calorimetry (DSC) 22 3.6. Fourier transform infrared (FT-IR) 24 3.7. In vitro release study 26 4. Conclusion 28 References 30 -국문요약- 36 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | Chitosan-coated Lipid-Polymer Hybrid Nanoparticles for Oral Delivery of Nadroparin | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.alternativeName | Hui-Won Cho | - |
| dc.contributor.department | 일반대학원 약학과 | - |
| dc.date.awarded | 2021. 2 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 1202975 | - |
| dc.identifier.uci | I804:41038-000000030672 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/common/orgView/000000030672 | - |
| dc.subject.keyword | 경구 전달 | - |
| dc.subject.keyword | 고체 리피드 나노입자 | - |
| dc.subject.keyword | 나드로파린 | - |
| dc.subject.keyword | 지연된 방출 | - |
| dc.subject.keyword | 키토산 | - |
| dc.subject.keyword | 하이드로겔 중심부 | - |
| dc.description.alternativeAbstract | The oral dosage form is the preferred route for drug delivery because it allows to enhance patient compliance as well as to provide advantages in the management of diseases. Nadroparin as a low molecular weight heparin (LMWH) was only administrated by parenteral routes since it has characteristics such as high molecular size, high water solubility, and poor permeation in intestinal wall. In this study, chitosan-coated lipid-polymer hybrid nanoparticles (C-LPNs) were produced for the oral delivery of nadroparin. Hydrogel core was used as an alternative of the properties of lipid nanoparticles that had a limit on the amount of encapsulation of hydrophilic drugs. Drugs protection at acidic conditions in stomach is an important point that oral delivered nanoparticles should have. Chitosan coating can reduce the aggregations of nanoparticles under gastric condition, providing better stability. The modified W/O/W double emulsion method was applied in a suitable production with the properties of the particle and the activity of the drug. During the process of obtaining lipid-polymer hybrid nanoparticles (LPNs), C-LPNs was produced by adding the chitosan solution. C-LPNs were composed of the hydrophilic core and the lipids shell, and then chitosan was coated by physical absorption and surface interaction. Physicochemical properties of optimized formulations were evaluated by the measurements of particle size, zeta-potential, and encapsulation efficiency. Stability in simulated gastric condition, morphology of C-LPNs, and in vitro drug release were investigated. Stability of the optimized formulation with chitosan coating has improved values both in particle size and zeta potential. The release studies were executed in phosphate buffered saline (pH 7.4) in shaking water bath with 100 rpm at 37°C for 72 h. The cumulative release was 74.24% of C-LPNs compared to 81.45% of LPNs within 72 h, and C-LPNs showed the sustained release rate. C-LPNs might be a promising approach for oral formulation of biomolecules. | - |
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- Graduate School of Ajou University > Department of Pharmacy > 3. Theses(Master)
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