나노의학적 응용을 위한 양친매성 6-arm 폴리락티드 폴리에틸렌글리콜 공중합체
Amphiphilic 6-arm PLLA-PEG block copolymers for nanomedical applications
- 주제(키워드) micell , sustained release , block copolymer , PLLA-PEG , CPEG
- 주제(KDC) 570
- 주제(DDC) 660
- 발행기관 아주대학교 일반대학원
- 지도교수 박기동
- 발행년도 2007
- 학위수여년월 2007. 2
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 본문언어 영어
초록/요약
Polymeric micelles(PMs) using amphiphilic block copolymers have been widely studied due to their potential application in drug delivery system because they are capable of forming micelle in aqueous solutions. Most of materials for polymeric micelles are di or tri block copolymers or comb-type graft copolymers that have a hydrophilic on hydrophobic back bone. This thesis is a study about amphiphilic 6-arm Poly(L-lactide)-poly(ethylene glycol) (6-arm PLLA-PEG) block copolymer synthesis and preparation of micelle and thermosensitive phase transition polymer aqueous solution using the 6-arm PLLA-PEG block copolymer and observation of sol-gel transition behavior and in vitro drug release for controlled drug release. 6-arm PLLA polymer was synthesized by the ring opening polymerization of L-lactide with dipentaerythritol using stannous octoate as a catalyst, and 6-arm PLLA-PEG block copolymer was prepared by coupling carboxylated MPEG with 6-arm PLLA using DCC/DMAP as coupling agents. Physicochemical properties of these polymers were examined by ¹H-NMR, FT-IR and GPC. The critical micelle concentration (CMC) of 6-arm PLLA-PEG block copolymer was determined by fluorescence probe technique using pyrene. The diameters of 6-arm PLLA-PEG micelle in number-averaged scale were observed around 90~100 nm, resulting in increases in the diameter of IMC (Indomethacin)-loaded micelle (ca. 100~136 nm). In vitro release test, the IMC release profile is no initial burst and sustained released from micelle. The sol-gel transition behavior was arisen around body temperature at 40~45 wt % aqueous solution but LCST (Lower critical solution temperature) is not appeared. The amphiphilic 6-arm PLLA-PEG block copolymers have six living end groups. The living end group is useful to introduce a bioactive moiety such as heparin, folic acid, fluorescence molecular probe and cell specific binding moiety etc. Our results suggest that amphiphilic 6-arm PLLA-PEG block copolymers micelle have potentials for nanopharmaceutical and nanomedical applications such as drug delivery system and molecular imaging and gel matrix for tissue regeneration and repair.
more목차
Ⅰ. INTRODUCTION = 6
A. What is nanomedicine? = 6
B. The field of nanomedicine = 9
C. Polymeric micelles = 13
1. Chemical nature of polymeric micelles = 14
2. Mechanism of micelle formation = 17
3. Pharmaceutical applications = 19
D. Biodegradable polymer = 25
1. Poly(lacltide) (PLA) = 26
E. Objectives = 28
Ⅱ. MATERIALS AND METHODS = 29
A. Materials = 29
B. Synthesis of 6-arm PLLA-PEG block copolymer = 29
1. Synthesis of 6-arm poly(L-lactide) acid(6-arm PLLA) = 29
2. Preparation of carboxylated Monomethoxy poly(ethylene glycol) (CMPEG) and carboxylated poly(ethylene glycol) (CPEG) = 31
3. Synthesis of 6-arm PLLA-PEG and 6-arm PLLA-MPEG = 33
C. Characterizations of 6-arm PLLA, 6-arm PLLA-PEG and 6-arm PLLA-PEG = 35
D. Sol-gel transition behavior test = 35
E. Preparation and characterization of micelle = 36
1. Determination of critical micelle concentration (CMC) = 36
2. Preparation of drug loaded micelle = 37
3. Size distribution = 37
F. Measurement of drug loading amount and efficiency = 38
G. Release kinetics test = 38
Ⅲ. RESULTS AND DISCUSSION = 40
A. Synthesis and characterization of 6-arm PLLA = 40
B. Preparation and characterization of carboxylated MPEG and PEG = 42
C. Synthesis and Characterization of 6-arm PLLA-PEG block copolymers and 6-arm PLLA-PEG block copolymers = 44
D. Sol-gel transition behavior = 49
E. Micelle preparation and characterization = 51
1. Critical micelle concentration (CMC) = 51
2. Size distribution = 52
3. Drug loading amount and efficiency = 53
4. In vitro release profiles = 53
Ⅳ. CONCLUSIONS = 55
Ⅴ. REFERENCES = 57
