利用超臨界二氧化碳製備生物可分解之溫度/pH敏感性核殼共聚物

Abstract

智慧型高分子目前被廣泛的應用於各個研究領域，其中pH值敏感性及溫度敏感性材料可應用於藥物控制釋放和生物科技材料上，此材料本身如果具備生物可分解性，將更增加其應用價值，本研究選擇之溫度敏感性材料poly[(2-(2-methoxyethoxy)ethyl methacrylate)-co-(oligo(ethylene glycol) methacrylate)] [P(MEO2MA-co-OEGMA)]和pH值敏感性材料[(polydimethylsiloxane)-g-(polyacrylate)] (PDSM-g-PAA)皆具有相當好的生物可分解性，而且此溫度敏感性材料可藉由改變組成調整低臨界溶解溫度(lower critical solution temperature, LCST)值，增加材料的應用性。一般合成方法所使用的有機溶劑、觸媒和起始劑對於環境有較大的衝擊性，並且會造成後續產物分離程序上的困難，因此本研究利用超臨界二氧化碳技術進行此溫度敏感性材料的合成，並進一步加入pH值敏感性材料與其交聯，提高材料之功能性。 本研究結果顯示在超臨界二氧化碳系統下的確可以合成此溫度敏感性材料，並且經由UV分析後，確認此材料可藉由組成不同而改變LCST值。在進一步加入pH值敏感性材料後，也可由FTIR、TGA、TEM、UV等儀器分析以及膨潤度(swelling ratio)測試，確認兩材料的確有產生交聯，結構上具有core-shell的型態，並且敏感性顯示在溫度35℃以上和pH值7以上會產生明顯的狀態變化；製程上，亦可經由簡單的洩壓得到乾燥的產物，簡化分離程序，同時有機溶劑的使用量大幅減少，有效降低對環境的汙染性。另一方面，本研究亦針對操作參數對於產物分結構、粒徑大小、顆粒分散性以及對溫度和pH值的敏感性進行分析，決定最佳的操作條件為壓力300bar，溫度100℃，反應時間4小時，反應物組成為60wt%的PDMS-g-PAA。從SEM圖中觀察到原本不規則片狀的PDMS-g-PAA顆粒經由此反應程序可合成接近球狀的(PDMS-g-PAA)-g-P(MEO2MA-co-OEGMA)，進一步利用imageJ軟體分析圖中顆粒大小後，發現PDMS-g-PAA原始粒徑為11μm，反應後產物粒徑最小可降至0.15μm。

The supercritical carbon dioxide is applied in this research to synthesize the temperature/pH value sensitive biodegradable core-shell smart copolymer materials. Supercritical fluid technology has the advantages of reducing significantly the amount of solvent in traditional process. It can also avoid the oxidation of initiators, and simplify the following separation steps. The dry products can be obtained after depressurization and the desired smart copolymer material is used for the controlled release of drugs, or the phase separation for protein recovery. In this study, poly[(2-(2-methoxyethoxy)ethyl methacrylate)-co-(oligo(ethylene glycol) methacrylate)] [P(MEO2MA-co-OEGMA)] with great temperature-sensitive properties was synthesized by polymerization reaction in the medium of supercritical carbon dioxide (scCO2). Its LCST (lower critical solution temperature) value was changed by adjusting the compositions of monomers. Furthermore, the copolymers with fine temperature- and pH-sensitive properties have been obtained through the single step supercritical carbon dioxide chemical reaction process for the polymerization of temperature-sensitive material and cross-linking with the [(polydimethylsiloxane)-graft-(polyacrylate)] (PDMS-g-PAA). The particles transform between swelling and shrinking with the temperature and pH value limits of 35℃and 7, respectively. The core-shell structure was observed by TEM images. The characteristics of the products were examined using UV, FTIR, TGA, SEM, and swelling ratio analysis. The optimal process parameters in the synthesis of smart core-shell copolymers were reported in this study. The particles with great pH/T-sensitive properties, smaller average particle size and size distribution were obtained at the following operating condition: T=100℃, P=300bar, Reaction Time=4hr, Reactants composition=60wt% PDMS-g-PAA. From SEM images and the analysis of image J software, we observed the morphology of original PDMS-g-PAA particle was amorphous with an approximately particle size = 11μm . After reaction process, the grafted copolymer particle became globular shape. The particle size was reduced to 0.15μm.