單甲氧基聚乙二醇-聚己內酯團聯共聚 物合成及其接枝於2-羥乙基纖維素材 料之藥物釋放應用研究

Synthesis of Poly( ethylene glycol )-g- Poly(ε-Caprolactone ) block copolymer and Grafting reactions to 2-Hydroxyethyl cellulose for drug delivery application

陳釗炫(Chao-Hsuan Chen)

指導教授 ： 謝明發

中原大學/工學院/醫學工程研究所/碩士(2007年)

https://doi.org/10.6840/cycu200700893

摘要

本研究中，首先以單甲氧基聚乙二醇為起始劑對己內酯單體做開環聚合反應合成單甲氧基聚乙二醇-聚己內酯團聯共聚物(mPEG-PCL)。mPEG-PCL以琥珀酸酐改質為末端具有羧酸之化學結構並接枝於2-羥乙基纖維素(2-hydroxyethyl cellulose)側鏈得到具有梳狀結構的mPEG-PCL-g-2-hydroxyethyl cellulose團聯共聚物。使用氫質子核磁共振儀、紅外線光譜儀、掃描熱分析儀及凝膠滲透層析儀分析該團聯共聚物的結構與組成。由於該團聯共聚物具有雙極性(amphiphilic)，所以本研究利用1,6-diphenyl-1,3,5-hexatriene為螢光探針測量其臨界微胞濃度(CMC)並探究其形成微胞的行為，結果顯示團聯共聚物接枝纖維素後仍可形成微胞並且結構穩定，CMC為2.2×10-1 wt%~9.9×10-3 wt%。該團聯共聚物配製成5%、10%之水膠並以冷凍乾燥形成具有孔洞性薄膜，孔徑大小介於64~132.5微米；掃描式電子顯微鏡中發現5 wt%薄膜表面的孔洞較致密且分佈較均勻。在薄膜水中溶解度試驗中，純mPEG-PCL-g-cellulose的薄膜僅能在水中維持90分鐘。為了維持水中結構安定性，以該團聯共聚物水膠與末端改質壓克力的PEG-HEMA，並以AIBN加熱形成交互穿刺網狀結構的薄膜，結果顯示5 wt％薄膜混合10 wt% PEG-HEMA以及10 wt%薄膜混合20 wt% PEG-HEMA的可在水溶液中維持結構完整達七天以上。
本研究合成之團聯共聚物以纖維素為主鏈，導入雙性聚乙二醇與己內酯團聯共聚物(PEG-PCL)於纖維素側鏈作為藥物載體，預期可以應用於藥物釋放及組織工程。

關鍵字

梳狀分子結構 ； 己內酯 ； 2-羥乙基纖維素 ； 雙性團聯共聚物 ； 甲氧基聚乙二醇

並列摘要

In this study, methoxy-(polyethylene glycol)-block-poly(-caprolactone) amphiphilic diblock copolymers (mPEG-PCL) were synthesized using ring-opening polymerization of ε-caprolactone. To produce a comb-like structure, mPEG-PCL was reacted with succinic anhydride and then grafted onto the side chain of 2-hydroxyethyl cellulose. The structure of the mPEG-PCL-g-2-hydroxyethyl cellulose copolymers were characterized by 1H NMR, IR spectroscopy, differential scanning calorimeter (DSC) and gel permeation chromatograph (GPC). The Tm of the mPEG-PCL-g-2-hydroxyethyl cellulose copolymers were 109 oC. The characteristic peaks of PCL, such as carbonyl stretching (1725 cm−1) and CH stretching (2945 cm−1) peaks, were observed by IR. The mPEG-PCL and mPEG-PCL-graft-cellulose copolymers can form micelles and the critical micelle concentrations (CMC) were 9.9×10-3 wt%, 4.5×10-3 wt% and 2.2×10-1 wt% for mPEG5000-PCL3527, mPEG5000-PCL3690-g-cellulose and mPEG550-PCL5684-g-cellulose, respectively, determined by 1,6-diphenyl-1,3,5-hexatriene as Fluorescence Probe. The porous membranes of 5% and 10% mPEG-PCL-graft-cellulose hydrogels were prepared using freeze drying method. The pore size were about 60~132.5 μm. The membrane of 5% showed dense pore as observed in SEM. In Solubility test, pure mPEG-PCL-g-cellulose membrane only can maintain the structure integrity for 90 minutes in the water. In order to improve the stability of the membranes, the hydrogel were mixed 5% and 10% HEMA-end caped PEG (PEG-HEMA) and formed interpenetrating network by heating with thermal initiator AIBN. As a result, the modified membranes can maintain structure integrity for seven days. The PEG-PCL side chain of cellulose were as drug carrier so that the copolymers were supposed to use in drug release and tissue engineering.

並列關鍵字

ε-caprolactone ； amphiphilic diblock copolymers ； 2-hydroxyethyl cellulose ； brush structure. ； methoxy poly(ethylene glycol)

參考文獻

[1] G. D.Winter, Formation of the scab and the rate of epitheliasation of superficial wounds in the skin of the yung domestic pig. Nature, 1963, 293-294.

[3] A. B. Lugao. S. M. Malmonge. Use of radiation in the production of hydrogels. NIMB, 1986, 185, 37-42.

[4] S. Y. Lin, K. S. Chen, L. R. Chu. Design and evaluation of drug-loaded wound dressing having thermoresponsive. absorptive and easy peeling properties. Biomaterial. 2001. 22. 2999-3004.

[5] W. Meier, U. Hoppe, Texture analysis of human skin, Skin Pharmacology, 1995, 8, 252-256.

[6] S. Enoch, D. J. Leaper. Basic science of wound Healing. BASIC SCIENCE. 2005.