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  • 學位論文

Structure Design of Thermosensitive Oligopeptide Hydrogel fro Drug Delivery

指導教授 : 朱一民

摘要


本論文第一部分為藉由改變在寡聚胺基酸上的微少官能基, 改變分子的奈米排列及流變特性, 進而得到劇烈的溫感性水膠. 另一個工作為呈現一個新型的感溫型且具生物相容性的水膠材料, 並將其攜帶抗體藥物來達到藥物緩釋的效果. 從累積性的藥物釋放數據, 可以知道在一個月內, 藥物從水膠內可釋放出90%. 而且這個水膠材料在體外試驗中無明顯毒性. 此論文不但說明如何藉由改變官能基來改變胜肽的二級結構, 進而改變分子的奈米排列以及流變特性(第三章); 而且也確認了一個新型的生物良好性水膠材料,它有用在包覆抗體並達到緩釋目的的潛力(第四章). 總言, 這寡聚型胜肽胺基酸水膠, 在這篇論文被描述出, 並提出可應用在藥物傳輸.

關鍵字

溫感性 水膠 胜肽 二級結構 藥物傳輸

並列摘要


The first part of this thesis focuses on a slight change in the functional group of the oligopeptide block incorporated into the Poloxamer triblock copolymer that led to drastically different hierarchical assembly behavior and rheological properties in aqueous media for the application as thermo-sensitive hydrogel. Another work presents a new thermosensitive biocompatible oligopeptide-containing hydrogel which is novel for carrying antibody drug - bevacizumab with extended release. The accumulative extended release of bevacizumab in vitro from hydrogel was approximately 90% over a period of one month. Moreover, the in vitro cytotoxicity of oligopeptide-containing Poloxamer copolymer aqueous solution was found to be low on the human retinal pigment epithelial cells. These results not only resolve how the change of the peptide functional group would modify the secondary structure supramolecular assembly behavior and rheological properties of the block copolymer (chapter 3), but also identify a new biocompatible thermo-sensitive hydrogel with low critical gelation concentration (CGC), which may be used in typical diffusion-controlled drug release (chapter 4). In summary, the oligopeptide thermosensitive hydrogel can be used in the field of drug delivery is described in this thesis.

參考文獻


[1] Hoare TR, Kohane DS. Hydrogels in drug delivery: Progress and challenges. Polymer. 2008;49:1993-2007.
[2] Misra GP, Singh RSJ, Aleman TS, Jacobson SG, Gardner TW, Lowe TL. Subconjunctivally implantable hydrogels with degradable and thermoresponsive properties for sustained release of insulin to the retina. Biomaterials. 2009;30:6541-7.
[3] Al-Abd AM, Hong K-Y, Song S-C, Kuh H-J. Pharmacokinetics of doxorubicin after intratumoral injection using a thermosensitive hydrogel in tumor-bearing mice. Journal of Controlled Release. 2010;142:101-7.
[4] Sivakumaran D, Maitland D, Hoare T. Injectable microgel-hydrogel composites for prolonged small-molecule drug delivery. Biomacromolecules. 2011;12:4112-20.
[5] Turturro SB, Guthrie MJ, Appel AA, Drapala PW, Brey EM, Pérez-Luna VH, et al. The effects of cross-linked thermo-responsive PNIPAAm-based hydrogel injection on retinal function. Biomaterials. 2011;32:3620-6.

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