서방형 약물 방출이 가능한 마이크로스피어/하이드로겔 복합 주사 제제 개발
Injectable dexamethasone-loaded microsphere/hydrogel combination system for sustained drug release
- 주제(키워드) microsphere , hydrogel
- 발행기관 아주대학교
- 지도교수 김문석
- 발행년도 2018
- 학위수여년월 2018. 2
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000027136
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Microsphere system have been used drug delivery systems for a variety of drugs. Microsphere systems, however, may release the drug quickly during the first day. The initial burst of drug release may results in lower therapeutic efficiency and cause side effects. We hypothesized that microsphere/hydrogel combination systems can refrain the initial burst of drug release. To test this hypothesis, we prepared the microspheres using a monoaxial one-nozzle ultrasonic atomizer with an encapsulation efficiency of about 80% and microsphere particle size of about 57 µm. Microsphere/hydrogel combination formulation were prepared by mixing drug-loaded microspheres and Pluronic (PH) and crosslinked hyaluronic acid (HA). All formulations were manufactured as solution forms and changed to gel when injected into the subcutaneous of Sprague-Dawley (SD) rats. While confirming that the persistence of injectable materials in vivo, we confirmed that the initial burst of drug release was suppressed by in situ forming hydrogels. The maintenance period of the in situ forming hydrogel is a very important factor in drug release period. We conclude that the properties of hydrogels affect the inhibition of initial release of drug and sustained drug release. In conclusion, we believe that the current research is an effective drug delivery system and that will be useful drug delivery system in the future.
more목차
1. Introduction 1
2. Materials and Method 5
2.1 Materials 5
2.2 Preparation of Dex-loaded microspheres (Dex-M) 6
2.3 Drug encapsulation efficiency of Dex-M 6
2.4 Size measurement of Dex-M 7
2.5 Preparation of TET-HA and TCO-HA hydrogel formulation 8
2.6 Preparation of NIR-labelled TET-HA and NIR-labelled TCO-HA hydrogel formulation 8
2.7 Preparation of NIR-labelled PH hydrogel formulation 9
2.8 Preparation of the Dex-M, Dex-M-loaded PH, and Dex-M-loaded HA 10
2.9 Rheological measurements of the Dex-M-loaded PH, and Dex-M-loaded HA 10
2.10 In vitro Dex release 11
2.11 In vivo Dex release 11
2.12 Fluorescence images on in vivo 13
2.13 Scanning electron microscope (SEM) measurements 14
2.14 Histological analysis 15
2.15 Statistical analysis 17
3. Results and Discussion 18
3.1 Preparation of Dex-M 18
3.2 Preparation of injectable Dex-M-loaded hydrogel formulations 22
3.3 Characterization of injectable Dex-M-loaded hydrogel formulations 25
3.4 In vitro Dex release from injectable formulations 27
3.5 In vivo persistence of injectable materials 30
3.6 In vivo Dex release from injectable formulations 34
3.7 In vivo SEM images of injectable materials 37
3.8 Histology of injectable materials 39
4. Conclusion 43
5. References 44
ABSTRACT (IN KOREAN) 50
LIST OF PUBLICATIONS 51
LIST OF PRESENTATIONS 52
LIST OF PATENTS 53
