聚丙二醇兩性分子之鏈長與親水基團對油酸甘油酯之液向型液晶相行為之影響

The effect of chain length and hydrophilic head groups containing poly(propylene glycol) on the formation of lyotropic liquid phases of glyceryl monoleate

尤建智(Jian-Zhi You)

指導教授 ： 歐信宏

義守大學/理工學院/化學工程學系暨生物技術與化學工程研究所/碩士(2018年)

摘要

液向型液晶之Reversed bicontinuous cubic phase (V2)與Reversed hexagonal phase (H2)的液晶結構中具有特殊的奈米水分子通道，應用於藥物載體時，可透過此特性使藥物緩慢釋放，藉以達到延長藥效時間的效果。由文獻中可知Glyceryl monooleate (GMO)在高含水量環境下能形成V2及H2 phase。本研究以Poly(propylene glycol)為基礎設計了三種不同親水基團兩性分子：Poly(propylene glycol)-OH、Poly(propylene glycol)-acid及 Poly(propylene glycol)-glyerol (PPG-Gly)。是將Poly(propylene glycol)monobutyl ether作為疏水端長鏈而合成的兩性分子，由於PPG長鏈側邊具有多個甲基分支結構，可以提高疏水端截面積，進而使晶相往Reversed phase堆積，再藉由分子量的不同來控制PPG-OH疏水端長鏈，進而晶相變化，並觀察其相行為。
使用不同分子量的PPG-OH與Succinic anhydride反應後得到活性較高的PPG-Acid，再將PPG-Acid與Solketal反應後得到PPG-Solketal，再透過斷環反應，將環狀結構打開就可得到所設計之不同分子量的PPG-GLY。
經過偏光顯微鏡的觀察，PPG-GLY與水混合時無法形成H2晶相，推測原因是因為PPG-GLY分子太過舒柔所導致。因此，以GMO為主體添加PPG-OH、PPG-Acid、PPG-Gly來探討晶相變化。GMO在高含水量時，朝向H2及V2晶相堆積，而自行合成的GMO具有異構物2- monoolein，導致在高溫環境下無法形成H2晶相。因此透過控制不同分子量的PPG-OH(1000、2500)、PPG-Acid(340、1000、2500)、PPG-Gly(1000、2500)來調控H2晶相之形成，PPG-Acid 340因為與GMO分子之鏈長過於接近，無法對GMO之H2晶相生成有所幫助，而分子量1000以及2500之疏水端鏈長皆比GMO分子長，添加在GMO中可以填補H2晶相堆積的空白區域，使整體利於H2晶相的生成，同時隨著添加量的提高，H2晶相的生成溫度也會下降，溫度生成之範圍亦會改變，當PPG-OH 1000之添加量由1mole%提高至6mole%，H2晶相存在之溫度範圍則由51°C ~88°C降低至45°C ~62°C；PPG-Gly之添加量由1mole%提高至6mole%，H2晶相存在之溫度範圍則由77°C ~92°C降低至45°C ~70°C。改變親水基團亦會影響H2晶相之形成，PPG-Acid之親水基團較難與GMO之glycerol有效堆疊，以致H2晶相形成較不穩定。反之，PPG-OH、PPG-Gly之親水基團則較為柔軟有利於與GMO形成均勻混合，因而有助於H2晶相的穩定發展。

關鍵字

none

並列摘要

In order to prepare a nonlamellar lyotropic liquid crystalline structure, especially reverse bicontinuous cubic phase (V2) and reverse hexagonal phase (H2), amphiphiles (PPG-Gly 340 and 1000; PPG-Glc 340, 1000, and 2500) containing poly(propylene glycol)s (PPG-OH) of different molecular weights (340, 1000 and 2500) as hydrophobic chains and glycerol or glucosamine as head groups were synthesized and investigated by optical microscopy and small angle X-ray scattering.
The proposed amphiphiles were synthesized firstly by the reaction of poly(propylene glycol) monobutyl ether with succinic anhydride to convert the hydroxyl end groups to carboxylic acid. For PPG-Gly, the thus-formed acid was connected with solketal by ester linkage and the protecting groups were removed by acid. PPG-Glc was synthesized by activating the thus-formed acid with N-hydroxysuccinimide and then be amidated with glucosamine.
For PPG-Gly 340 and PPG-Gly 1000, no lyotropic liquid crystalline phase could be observed probably due to the flexibility of PPG-OH. The effect of poly(propylene glycol) on the developments of reverse bicontinuous cubic phase (V2) and reverse hexagonal phase (H2) was further examined by the mixing of PPG-Gly with glyceryl monooleate (GMO), which has been well studied. The addition of PPG-Gly to GMO expedites the lamellar-Ia3d (V2)-Pn3m (V2) transformation of the hydrated GMO. Poly(propylene glycol)s of different chain lengths show rather different effects on both the phase behavior and the dimension of the structure. The Pn3m lattice parameter can be reduced by more than 20% on the addition of PPG-Gly1000. In contrast, the addition of PPG-Gly 340 increases the dimension by less than 5%. This result is explained by the hydrophobic chain splay. From polarizing optical microscopy, the addition of PPG-Gly 1000 to GMO enhances the formation of H2 phase substantially. The appearance of the H2 phase lasts for a temperature range of ca. 23℃. It was also found that the H2 phase coexists with the Pn3m phase and does not disappear at the same temperature, indicating a distribution of compositions of the hydrated PPG-Gly 1000/GMO mixtures.
In contrast to PPG-Gly, PPG-Glc 340 exhibits Lα、V2、H2 phases at 20 H2O wt%. It indicates that a strong head group interaction is required to develop lyotropic liquid crystalline phase for amphiphiles containing PPG-OH. The formation of liquid crystalline phase behavior was disturbed at high water content (~above 40wt%) because of the higher solubility of PPG-Glc 340 in water. Hydrated PPG-Glc 1000 and PPG-Glc 2500 cannot display liquid crystalline phases. The effect of chain length was examined by the addition of PPG-Glc 1000 and PPG-Glc 2500 to PPG-Glc 340 at 20 H2O wt%. The addition of PPG-Glc 1000 to PPG-Glc 340 enhances the formation of H2 phase substantially. On the other hand, H2 phase cannot be observed on the addition of PPG-Glc 2500. These results show that a suitable chain length is required for the formation of H2 phase.

並列關鍵字

none

參考文獻

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