Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/3796
標題: 利用脂質修飾葡萄聚醣及聚麩胺酸摻混製備高分子液胞與結構探討
Polymer Vesicles from Assembly of Mixture of Lipid-Modified Dextrans and Poly(r-glutamic acid)s and their Structural Characterization
作者: 陳俞彣
Chen, Yu-Wen
關鍵字: poymer vesicle
高分子液胞
solvent replacement
Dextran
poly glutamic acid
雙性高分子
溶劑置換法
摻混
葡萄聚醣
聚麩胺酸
出版社: 化學工程學系所
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摘要: 在本研究中使用兩種不同脂質共聚合高分子,葡萄聚醣-硬酯醇(dextran-g-octadecanol, 簡稱DO高分子)與聚麩胺酸-二硬酯酸甘油脂Poly(γ-glutamic acid-co-distearin glutamate)製備高分子液胞,並探討其摻混比例對高分子液胞結構之影響。 首先利用硬酯醇(Octadecanol)改質葡萄聚醣(dextran),透過轉酯化反應將脂質共價鍵結至葡萄聚醣鏈段上得葡萄聚醣-硬酯醇(dextran-g-octadecanol),並利用核磁共振氫譜儀(1H NMR)及紅外線光譜儀(FTIR)鑑定改質率,改質比例為20mol%之高分子簡稱為DO20。另一方面,製備Poly(γ-glutamic acid-co-distearin glutamate)是先以NHS活化聚麩胺酸,並於側鏈修飾二硬酯酸甘油脂(distearin),其脂質修飾比例為15mol%,在此簡稱為PGA-d15。 高分子DO20利用溶劑置換法搭配不同初始水量的添加,可得不同尺寸大小之高分子液胞,由1H NMR、DLS及TEM影像圖分析雙性高分子於不同DMSO/H2O共溶劑比例下排列情形,當水加入高分子DMSO溶液時,雙性高分子的脂質碳鏈因溶解度的降低,疏水作用力提升,驅使雙性高分子以水為核心,產生微相分離,當初始水量達到臨界水含量(Critical water content,CWC)時會形成穩定的高分子液胞結構,且液胞粒徑不因溶劑置換而有差異。根據SLS之測量結果,其Rg/Rh比值趨近於1,更可進一步證實添加不同初始水量所形成之結構皆為高分子液胞,且可穩定存在於水溶液中。 為增加高分子液胞之應用性與發展性,利用摻混DO20及PGA-d15製備摻混型高分子液胞,隨著PGA-d15摻混比例的增加,液胞粒徑逐漸變小,PGA-d15的加入會改變液胞排列之曲率,高摻混比例下 (PGA-d15為20 wt%),液胞曲率較高,粒徑較小。搭配上SLS之測量結果,證實摻混型高分子液胞之結構仍維持球型液胞結構。除此之外,由TEM影像圖證實可將水溶性物質(calcein)包覆於液胞內部,此高分子液胞不僅可包覆水溶小分子calcein與熊果素(arbutin),亦能包覆分子量較大的牛血清蛋白(BSA),大幅提升此高分子液胞於藥物載體應用上之潛力。
In this study, we have synthesized the biodegradable amphiphilic lipid-modified Dextrans (DO20) and Poly(r-glutamic acid)s (PGA-d15). These materials are obtained by partial transesterification of octadecanol and distearin. The chemical compositions of copolymers are precisely determined by 1H-NMR and FT-IR measurements. The dextran-based nanoparticles are attained by self-assembly of amphiphilic copolymers in DMSO/H2O co-solvents and then dialysis against water. Combining the results of 1H-NMR and dynamic light scattering (DLS) measurements, the size of nanoparticles can be controlled by adjusting the DMSO/H2O ratio during self-assembly of copolymers. According to the Rg/Rh ratios of the particles examined by static light scattering (SLS) are approximately 1.0, confirming strongly that the structure of assemblies is presented in vesicle-like form. Then, we mixed these two copolymers mentioned before with different ratios in the condition of fixed ratio of the DMSO/H2O. The vesicles are attained by self-assembly of mixed copolymers and then dialysis against pH 7.0 buffer solution. Here, we replace H2O with buffer solution, and it can make the glutamic acid moieties more stable. The results of DLS measurements show the size of mixed vesicles decrease with the rise of PGA-d15 in mixed ratio. For expanding the applications of polymer vesicles, we use small hydrophilic molecules and protein as probes to measure the efficiency of encapsulation. This study suggests these hydrophilic probes can be totally encapsulated inside the vesicles. As a result, these polymer vesicles have potential in drug delivery systems.
URI: http://hdl.handle.net/11455/3796
其他識別: U0005-0508201017274300
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-0508201017274300
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