丙烯酸/聚乙二醇甲基醚丙烯酸酯/明膠有機混成凝膠之製備及性質與其對生物相容性之研究

Studies on the Preparation and Properties of the (AA/PEGMEA/GELATIN) Organic Hybrid Hydrogels and Evaluation of their Biocompatibility

林宴夙(Yann-Su Lin)

指導教授 ： 李文福

大同大學/工程學院/化學工程學系所/碩士(2004年)

摘要

本研究為製備一系列丙烯酸(AA)/聚乙二醇甲基醚丙烯酸酯(PEGMEA)/明膠之有機混成水膠，該水膠係使用溶液聚合法及光與溶液二步聚合法製備而得。實驗結果顯示二步聚合法(光與溶液)，製得之水膠產率高，膠體的結構緻密，平衡膨潤度低。另此合成方法可有效改善溶液聚合法中明膠加入水膠之內產生相分離的現象；本文將討論明膠含量對其膨潤度、物理性質及藥物釋放行為的影響。
另一方面，由於明膠缺少良好機械性質，故使用Genipin和戊二醛與明膠進行交聯而形成互穿網狀結構IPN水膠，進而探討此IPN膠體的膨潤行為及機械性質。由實驗結果得知，以化學性交聯方法製得之互穿網狀結構膠體，其膠體結構較為緻密。此乃交聯劑中的醛基和明膠的胺基產生置換縮合反應，增加鍵結強度所致，改善明膠所缺少的良好機械性質。
在藥物釋放行為中，水膠能承載藥物於適當環境中進行藥物釋放，其影響因子包括:膠體的膨潤度、藥物溶質的分子大小、親水性等。本文係探討由AA/PEGMEA/Gelatin有機混成水膠和不同交聯劑二次交聯後水膠，對藥物釋放行為的研究。
擬適用於醫學之生物材料，對人體應無毒性的危害且材料能避免真菌感染的特質。故對AA/PEGMEA/Gelatin經不同交聯劑genipin及戊二醛進行交聯反應後，進行體外生物細胞毒性測試和抗微生物性試驗，結果顯示此類膠體不具毒性。

關鍵字

Hydrogel ； AA/PEGMEA/GELATIN ； Biocompatibility

並列摘要

A series of organic hybrid hydrogels for biomaterials were prepared from acrylic acid(AA), poly(ethylene glycol)9 methyl ether acrylate(PEGMEA), and gelatin by solution polymerization or a two-step polymerization (photopolymerization and solution polymerization). The results showed that copolymeric hydrogels (poly(AA-co-PEGMEA)) had high yield with two-step polymerization. At the same time, the gels have condensed structure and low swelling ratio. The effect of the gelatin amount added into the copolymeric gel composition on degree of swelling and mechanical properties and drug release behavior were also investigated in this study.
On the other hand, gelatin exhibits poor mechanical properties. To overcome these defects by chemical alteration, the hybrid hydrogels (poly(AA-co-PEGMEA)/gelatin) were further crosslinked with chemical crosslinking agent such as genipin (GP) and glutaraldehyte (GA) to form interpenetrating polymer network (IPN). Furthermore, the swelling kinetics, physical properties, and drug release of these novel IPNs were also investigated.
In the drug released, indomethacin and sulfanilamide were chosen as model drugs in this experiment. The factors that affect the drug release of the present IPN gels are the swelling ratio of the gels, molecular size and hydrophilicity of the drug solute, and concentration gradient of drug between inside and outside of the gels. Finally, the drug release of sulfanilamide was easier than indomethacin.
Biocompatibility of hydrogels was evaluated by cytotoxicity test and antimicrobial assessment. These gels should be nontoxic, fungal infected, and be able to antibacterial for medical applications. Hence, poly(AA-co-PEGMEA)/gelatin hydrogels were performed by in vitro cytotoxicity test and antimicrobial assessment. The results show that the present gels are nontoxic.

並列關鍵字

水膠 ； 丙烯酸/聚乙二醇甲基醚丙烯酸酯/明膠 ； 生物相容性

參考文獻

1. Kamath, K.; Park, K. Biodegradable Hydrogels in Drug Delivery, Adv Drug Deliv Rev 1993, 11, 59-84.

2. Park, K.; Shalaby, W. S. W.; Park, H. Biodegradable Hydrogels for Drug Delivery, Technomic Lancaster 1993.

3. Hoffman, S. A. Adv Drug Deliv Rev 2002, 43, 3–12.

5. Kikuchi, A.; Okano, T. Adv Drug Deliv Rev 2002, 54, 53-77.

6. Rathna, G. V. N. J Apply Polymer Sci 2004, 91, 1059–1067.