탈용매화 방법을 이용한 항암제 함유 젤라틴 올레인산 나노입자의 제조와 특성.
Preparation and Characterization of Anti-cancer drug loaded Gelatin-oleic Nanoparticles using Desolvation Method
- 주제(키워드) Gelatin-oleic conjugate (GOC) , Irinotecan , Protein conjugation , Desolvation method , Gelatin-oleic nanoparticles (GON).
- 발행기관 아주대학교
- 지도교수 이범진
- 발행년도 2013
- 학위수여년월 2013. 8
- 학위명 석사
- 학과 및 전공 일반대학원 약학
- 실제URI http://www.dcollection.net/handler/ajou/000000014738
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Abstract In this study, gelatin-oleic conjugate (GOC) was synthesized as a biomaterial for the preparation of anti cancer drug loaded nanoparticles (NP). Oleic acid (OA) was covalently bound to gelatin via EDC/NHS reaction in water-ethanol cosolvent to form GOC. Fourier Transform Infrared (FT-IR) spectroscopy and proton nuclear magnetic resonance (1H-NMR) study indicated the successful synthesis of GOC. The percentage of gelatin amino groups reacted with OA was up to 50% as determined by 2,4,6-trinitrobenzene sulfonic acid (TNBS) method. The gelatin-oleic nanoparticles (GON) were then prepared by desolvation method using glutaraldehyde and genipin as crosslinkers. Irinotecan was used as a model drug and loaded in GON by incubation and in-process adding method for comparison. Dynamic light scattering (DLS) and Transmission Electron Microscopy (TEM) data showed that the sizes of GON and irinotecan loaded GON (IRT-GON) were below 250 nm which is suitable for passive tumor targeting. The zeta potentials of GON and irinotecan loaded GON (IRT-GON) were below -20 mV which is inferred to be stable in suspension against the aggregation process. The incubation method was more suitable for drug loading because it did not affect the formation process of GON and thus did not increase the size of GON much compared to in-process adding method. The lipophilic property of oleic moiety in GOC increased the affinity between GOC molecules, thus reducing the amount of crosslinking agents needed to stabilize GON compared to gelatin nanoparticle (GN). Therefore, the toxicity of GON can be reduced and the applicability may be improved. These results showed that GOC is a promising material to prepare drug encapsulated NP and IRT-GON is a potential delivery system for cancer therapy.
more목차
CONTENTS
1. Introduction 1
2. Materials and methods 6
2.1. Materials 6
2.2. Preparation of IRT-GON 7
2.2.1. Synthesis of Gelatin-oleic conjugate (GOC) 7
2.2.2. Preparation of GON by desolvation method 9
2.2.3. Preparation of irinotecan loaded GON 9
2.3. Characterization of GOC, GON and IRT-GON 10
2.3.1. Fourier transform infrared spectroscopy (FT-IR) 10
2.3.2. Proton nuclear magnetic resonance (1H NMR) 10
2.3.3. Determination of the degree of acylation 11
2.3.4. Dynamic light scattering (DLS) 11
2.3.5. Transmission electron microscopy (TEM) 12
2.3.6. Drug loading content and encapsulation efficiency 12
3. Results and discussion 13
3.1. Synthesis of GOC 13
3.2. Identification of GOC 17
3.3. Determination of the degree of acylation 22
3.4. Physicochemical properties of GON 24
3.5. Physicochemical properties of IRN-GON 29
3.6. Drug loading content and encaspulation efficiency 31
4. Conclusions 32
5. References 33
