溫度敏感型胺基酸水膠具有良好的生物相容性，可以利用其在室溫下為溶液狀態，當注入人體內因為環境溫度變化而形成膠體，具有原位成膠的特性，作為藥物釋放載體或是組織工程支架等。本研究中所使用的材料是甲氧基化聚乙二醇-聚乙基左旋穀氨酸 (mPEG-PELG)，以甲氧基化聚乙二醇作為親水端，接合聚乙基左旋谷氨酸作為疏水端包覆抗癌藥物阿黴素之控制釋放。阿黴素是已經被廣泛應用於癌症治療的抗癌藥物，但是目前臨床上治療是以注射方式給藥，在體內瞬間濃度過高，會有超過造成中毒之疑慮，故本研究是希望利用甲氧基化聚乙二醇-聚乙基左旋穀氨酸 (mPEG-PELG)這種胺基酸材料特有的酵素降解特性達到穩定且長時間的緩慢釋放。
透過1H核磁共振儀確認成功合成mPEG-PELG共聚物，並藉由動態光散射儀、穿透式電子顯微鏡、掃描式電子顯微鏡、全反射傅立葉紅外線光譜儀、流變儀等儀器檢測其溫度敏感型胺基酸水膠表面結構、成膠機制、成膠特性。實驗結果顯示8 wt% mPEG-PELG在室溫狀態下呈現溶液狀態，在人體體溫下能夠形成膠體，透過高效液相層析儀確認其可以有效的包覆抗癌藥物阿黴素，且透過材料及細胞共培養實驗，結果顯示本材料具有良好的生物相容性。透過包覆抗癌藥物阿黴素的水膠與子宮頸癌細胞 (Hela cell) 進行培養的結果，確認藥物能釋放至培養液中，並有效的毒殺癌細胞。經過以上研究結果顯示，本材料相當具有潛力可以作為包覆抗癌藥物的載體。

Thermosensitive polypeptide hydrogel has a good biocompatibility, and it undergoes sol-to-gel transition as the temperature increases. Therefore, mPEG-PELG (Poly(ethylene glycol)-(Poly(γ-ethyl-ʟ-glutamate)) is promising to be used as an in-situ gelling vector for drug delivery and tissue engineering. Doxorubicin is a representative anthracycline antibiotic and one of the most widely used anticancer drugs. However, the chemotherapeutic compound induces strong side effects to human health, including nephrotoxicity and cardiotoxicity. In this study, we are copolymerizing poly (ethylene glycol) monomethyl ether and poly (ethyl-ʟ-glutamate) to form a thermosensitive polypeptide hydrogel. The objective of this research is to prolong the release time of Doxorubicin by the use of hydrogel.
The Nuclear Magnetic Resonance (1H-NMR) and Gel Permeation Chromatography (GPC). analyses indicate that Poly(ethylene glycol)-(Poly(γ-ethyl-ʟ-glutamate) (mPEG-PELG) copolymer was successfully synthesized. 8 wt% mPEG-PELG has a sol-gel transition temperature at 37 Celsius and has high degree of drug encapsulation. The cell viability test of MC3T3 cells also shows that mPEL-PELG has a good biocompatibility.The in vitro cytotoxicity test shows that the release of Doxorubicin from the mPEG-PELG hydrogel can efficeintly inhibit the growth of Hela cell.This study indicates that mPEG-PELG is a high potential drug carrier for emerging biomedical applications.

1.Hoare, T., Kohane, D.: Hydrogels in drug delivery: Progress and challenges. Elsevier, 49, 1993-2007 (2008).
2.Wichterle, O., Lim, D.: Hydrophilic Gels for Biological Use. Nature, 185, 117-118 (1960).
3.Kopecek, J.: Hydrogel biomaterials: A smart future? Elsevier, 28, 5185-5192 (2007).
4.Drury, J., Mooney, D.: Hydrogels for tissue engineering: scaffold design variables and applications. Elsevier, 24, 4337-4351 (2003).
5.Baipai, A., Shukla, S., Bhanu, S., Kankane, S.: Responsive polymers in controlled drug delivery. Elsevier, 33, 1088-1118 (2008).
6.Ebara, M., Kotsuchibashi, Y.,Narain, R., Idota, N., Kim, Y., Hoffman, J., Uto, K., Aoyagi, T.: Smart Biomaterials. Springer (2014).
7.Huynh, C., Nguyen, M., Lee,D.: Injectable Block Copolymer Hydrogels: Achievements and Future Challenges for Biomedical Applications. Macromolecules, 44, 6629-6636 (2011).
8.Nguyen, M., Alsberg, E.: Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine. Elsevier, 39, 1235-1265 (2014).
9.Chung, H.,Park, T.: Self-assembled and nanostructured hydrogels for drug delivery and tissue engineering. Elsevier, 4, 429-437 (2009).
10.Gupta, P., Vermani, K., Garg, S.: Hydrogels: from controlled release to pH-responsive drug delivery. Elsevier, 7, 569-579 (2002).
11.Boustta, M.,Colombo, P., Lenglet, S.,Poujol, S., Vert, M.: Versatile UCST-based thermoresponsive hydrogels for loco-regional sustained drug delivery. Elsevier, 174, 1-6 (2014).
12.Klouda, L.: Thermoresponsive hydrogels in biomedical applications: A seven-year update. Elsevier, 97, 338-349 (2015).
13.Jeong, B., Moon, H., Ko, D., Park, M., Joo, M.: Temperature-responsive compounds as in situ gelling biomedical materials. Chem. Soc. Rev, 41, 4860-4883 (2012).
14.Nguyen, M., Lee, D.: Injectable Biodegradable Hydrogels. Micromolecular Bioscience, 10, 563-579 (2010).
15.Yu, L.,Ding, J.: Injectable hydrogels as unique biomedical materials. Chem. Soc. Rev, 37, 1473-1481 (2008).
16.Yu, L., Chang, G., Zhang, H.,Ding, H.: Temperature‐induced spontaneous sol–gel transitions of poly(D,L‐lactic acid‐co‐glycolic acid)‐b‐poly(ethylene glycol)‐b‐poly(D,L‐lactic acid‐co‐glycolic acid) triblock copolymers and their end‐capped derivatives in water. Polymer Chemistry, 45, 1122-1133 (2007).
17.Jeong, B.,Kim, S., Bae, Y.: Thermosensitive sol–gel reversible hydrogels. Elsevier, 64, 154-162 (2012).
18.Lee, D.,He, C., Kim, S.: In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery. Elsevier, 127, 189-207 (2008).
19.Jeong, B.,Joo, M., Park, M., Choi, B.: Reverse thermogelling biodegradable polymer aqueous solutions. J. Mater. Chem., 19, 5891-5905 (2009).
20.Fairman, R., Akerfeldt, K.: Peptides as novel smart materials. Elsevier, 15, 453-463 (2005).
21.Jeong, B., Yun, E., Yon, B., Joo, M.: Cell Therapy for Skin Wound Using Fibroblast Encapsulated Poly(ethylene glycol)-poly(l-alanine) Thermogel. Biomacromolecules, 13, 1106-1111 (2012).
22.Jeong, B.,Yeon, B., Park, M., Moon, H., Kim, S., Cheon, Y.: 3D Culture of Adipose-Tissue-Derived Stem Cells Mainly Leads to Chondrogenesis in Poly(ethylene glycol)-Poly(l-alanine) Diblock Copolymer Thermogel. Biomacromolecules, 14, 3256-3266 (2013).
23.Huang, J., Hastings, C., Duffy, G., Kelly, H.,Raeburn, J., Adams, D., Heise, A.: Supramolecular Hydrogels with Reverse Thermal Gelation Properties from (Oligo)tyrosine Containing Block Copolymers. Biomacromolecules, 14, 200-206 (2013).
24.Cheng, Y., He, C., Xiao, C., Ding, J., Zhuang, X., Huang, Y., Chen, X.: Decisive Role of Hydrophobic Side Groups of Polypeptides in Thermosensitive Gelation. Biomacromolecules, 13, 2053-2059 (2012).
25.Chiang, P., Lin, T., Tsai, H., Chen, H., Liu, S., Chen, F., Hwang, Y., Chu, I.: Thermosensitive Hydrogel from Oligopeptide-Containing Amphiphilic Block Copolymer: Effect of Peptide Functional Group on Self-Assembly and Gelation Behavior. Langmuir, 29, 15981-15991 (2013).
26.Shinde, U., Moon, H., Ko, D., Jung, B., Jeong, B.: Control of rhGH Release Profile from PEG–PAF Thermogel. Biomacromolecules, 16, 1461-1469 (2015).
27.Cheng, Y., He, C., Xiao, C., Ding, J., Zhuang, X., Huang, Y., Chen, X.: Decisive Role of Hydrophobic Side Groups of Polypeptides in Thermosensitive Gelation. Biomacromolecules, 13, 2053-2059 (2012).
28.Das, D., Pal, S.: Modified biopolymer-dextrin based crosslinked hydrogels: application in controlled drug delivery. RSC Advance, 5, 25014-25050 (2015).
29.Branco, M., Schneider, J.: Self-assembling materials for therapeutic delivery. Elsevier, 5, 817-831 (2009).
30.Lin, C., Metters, A.: Hydrogels in controlled release formulations: Network design and mathematical modeling. Elsevier, 58, 1379-1408 (2006).
31.Cheng, Y., He, C., Ding, J., Xiao, C., Zhuang, X., Chen, X.: Thermosensitive hydrogels based on polypeptides for localized and sustained delivery of anticancer drug. Elsevier, 34, 10338-10347 (2013).
32.Zhu, H., Sarkar, S., Scott, L., Danelisen, I., Trush, M., Li, Y.: Doxorubicin Redox Biology: Redox Cycling, Topoisomerase Inhibition, and Oxidative Stress. React Oxyg Species (Apex), 1, 189-198 (2016).
33.Vejpongsa, C., Yeh, E.: Prevention of Anthracycline-Induced Cardiotoxicity. Journal of the American College of Cardiology, 64, 938-945 (2014).
34.Alhareth, K., Vauthier, C., Guetin, C., Ponchel, G., Moussa, F.: HPLC quantification of doxorubicin in plasma and tissues of rats treated with doxorubicin loaded poly(alkylcyanoacrylate) nanoparticles. Elsevier, 128-132 (2012).