利用靜電場製成水膠載體應用於組織工程與藥物傳輸系統

Electrostatic Force-derived Biopolymeric Hydrogel applied in Tissue Engineering and Drug Delivery System

張栩榮(Benjamin Teong)

指導教授 ： 郭士民

共同指導教授 ： 莊景文(Chin-Wen Chuang)

義守大學/電機資訊學院/電機工程學系/博士(2014年)

https://doi.org/10.6343/ISU.2014.00007

摘要

高分子材料褐藻酸、幾丁聚醣、明膠以及玻尿酸可藉由靜電場的作用（HVEFS或EFS）形成微粒、團藻型微粒以及奈米粒子。褐藻酸團藻微粒的探討記錄於part A而幾丁聚醣、明膠以及玻尿酸形成的奈米粒子則描述於part B。當褐藻酸團藻微粒包覆著兩種微粒各含有BSA以及CytC的時候，其藥物釋放行為不同於單一藥物的釋放。褐藻酸團藻微粒也可包覆bmMSCs和livHEPs (或是AML12）這兩種細胞。Live/Dead染色的結果顯示團藻微粒內的細胞在第14天的時候仍然活著，但是由於細胞被包覆於固體態的褐藻酸水膠內且無任何粘附質可供細胞貼伏，細胞的活性因而呈下降趨勢。此外，bmMSCs在共培養於團藻微粒得以趨化成類似肝細胞的現象，證明了褐藻酸團藻微粒在組織工程及藥物釋放的應用上是具有潛力的。在part B裡，油溶性抗癌藥物DHA以及CUR可藉由EFS的作用下與CHI、GEL以及HA奈米粒子結合成聚合物。癌細胞A549在48小時的藥物處理下，DHA-聚合物比單純DHA更具有引發細胞凋亡的效果。同樣的實驗A549細胞在CUR聚合物處理後，高CUR劑量可在短時間6小時內或以低CUR劑量在48小時處理後比單純CUR更具有抗癌效果。奈米粒子作為藥物載體可藉由內吞作用提升藥物進入細胞內，使其在應用於藥物釋放上具有潛力。

關鍵字

none

並列摘要

Polymeric biomaterials ALG, CHI, GEL and HA have been successfully made into hydrogels via HVEFS or EFS as in the form of microspheres, volvox-spheres or nanospheres. The study on ALG volvox-sphere was described in part A while CHI, GEL and HA nanospheres was in part B. ALG volvox-spheres are capable of encapsulating multiple types of drugs in which encapsulated BSA and CytC had shown different release behaviors compared to single drug encapsulation. Besides, ALG volvox-spheres were used as cells carrier for bmMSCs and livHEPs (or AML12). Live/dead staining showed that encapsulated cells remain viable on day 14 of culture but did not proliferate, probably due to the solid-gel phase of ALG and the absence of adherent ligands. Also, co-culturing allows the hepatic differentiation of bmMSCs, demonstrating that volvox-spheres have potential in the field of tissue engineering and drug delivery system. In part B, lipophilic anti-cancer drugs DHA and CUR were successfully incorporated into CHI, GEL and HA nanospheres separately via EFS in the form of aggregates. DHA-loaded aggregates were capable of enhancing the apoptotic effect toward A549 cells when compared to treatment with DHA alone in 48 h. CUR-loaded aggregates enhanced the anti-proliferation effect toward A549 cells by shorter duration of treatment in 6 h or lesser amount of drug in 48 h. Nanosphere as drug carrier facilitate the penetration into cell membrane by endocytosis, serving great potential as drug delivery systems.

並列關鍵字

none

參考文獻

[1] O. Şanlı, N. Ay, and N. Işıklan, "Release characteristics of diclofenac sodium from poly(vinyl alcohol)/sodium alginate and poly(vinyl alcohol)-grafted-poly(acrylamide)/sodium alginate blend beads," European Journal of Pharmaceutics and Biopharmaceutics, vol. 65, pp. 204-214, 2// 2007.

[2] F. d. S. G. S, W. RG, and D. A., "Two new staining procedures for quantitative estimation of proteins on electrophoretic strips.," Biochim Biophys Acta. , vol. 71, pp. 377-391, 1963.

[3] A. Haque, B. Hexig, Q. Meng, S. Hossain, M. Nagaoka, and T. Akaike, "The effect of recombinant E-cadherin substratum on the differentiation of endoderm-derived hepatocyte-like cells from embryonic stem cells," Biomaterials, vol. 32, pp. 2032-2042, 3// 2011.

[4] H.-Y. Li, Y. Chien, Y.-J. Chen, S.-F. Chen, Y.-L. Chang, C.-H. Chiang, et al., "Reprogramming induced pluripotent stem cells in the absence of c-Myc for differentiation into hepatocyte-like cells," Biomaterials, vol. 32, pp. 5994-6005, 9// 2011.

[5] W. Leong, T. T. Lau, and D.-A. Wang, "A temperature-cured dissolvable gelatin microsphere-based cell carrier for chondrocyte delivery in a hydrogel scaffolding system," Acta Biomaterialia, vol. 9, pp. 6459-6467, 5// 2013.