磁敏感性水膠的製備與特性及其在藥物釋放上的研究

Abstract

本論文中主要是發展一種生物可相容磁敏感性水膠(Ferrogel)，經由磁性氧化鐵奈米粒子與生物相容性明膠(gelatin)高分子混摻製備，並利用低毒性交聯劑genipin進行交聯而成。此水膠可利用外加磁場的操控而達到智慧型藥物控制釋放，可增加藥物釋放的精準性與應用性。磁敏感性水膠經由電子顯微鏡的觀察發現，明膠高分子可均勻包覆著氧化鐵奈米粒子。在藥物釋放與膨潤特性上，可經由交聯密度調控高分子鏈段的軟硬程度與分子孔洞的大小，進而得到不同膨潤速率與藥物釋放速率。而在外加直流電磁場的影響之下，磁敏感性水膠內的氧化鐵奈米粒子受到磁場的作用，造成吸附於高分子鏈段上鄰近的氧化鐵粒子彼此會形成微弱的作用力，使得水膠膨潤速率與藥物釋放速率會的明顯下降；此一作用力類似於高分子中，由氧化鐵奈米粒子所形成微弱的物理性磁性交聯點，而在磁場開啟時，此交聯點就形成，而在關閉磁場時，即會消失，利用此磁性操控的交聯點，可以控制水膠的藥物釋放速率。

進而經由化學共沈法使氧化鐵奈米粒子直接沈積於高分子中，發展出多孔磁敏感性水膠(Sponges)；而多孔磁敏感性水膠的孔洞大小大約於80□m到200□m之間，其內部的氧化鐵奈米粒子可生成至9.41％，其飽和磁性(saturation magnetization)為23.5emu/g，且在外部磁場的作用下，其磁敏感特性相當明顯，在磁場開啟時，多孔磁敏感性水膠的藥物釋放速率也有顯著的下降，適合作為細胞培養與組織工程上的應用。

The magnetic hydrogels were successfully fabricated by mixing gelatin hydrogels and Fe3O4 nanoparticles (ca. 40-60 nm) through chemically-cross-linked process using genipin (GP). The cross-sectional SEM observation demonstrates that the Fe3O4 nanoparticles were fairly uniformly distributed in gelatin hydrogels. Moreover, the in vitro release data reveal that it is able to control drug release profile of the resulting hydrogels by switching “on” or “off” mode of a given magnetic field. While applying magnetic fields to the magnetic hydrogels the release rate of vitamin B12 of the hydrogels decreased considerably, comparing to those while switching off the field, suggesting a “close” configuration of the hydrogels as a result of the aggregation of Fe3O4 nanoparticles. Based on this mechanism, a smart magnetic hydrogels can be potentially developed as drug delivery system and also used for the application of biomedical devices.

Magnetic sponges (ferrosponges) were successfully fabricated by biodegradable gelatin incorporating various amounts of iron oxide nanoparticles which were fabicated by in-situ co-precipitation process, and well dispersion in the sponges, leading to form ferrosponges. The resuting ferroscaaffolds have a uniform, black color and display an interconnected pore structure. The pore sizes of this ferrosponges distributed from 50□m to 200□m with different gelatin concentrations, as shown in scanning electron microscopy (SEM). The weight fractions (%) of iron oxide nanoparticles deposited in the ferrosponges changed by various ratio of precursor (Fe(II) and Fe(III) chloride) and gelatin contents, measured using thermo gravity analyzer (TGA). The result shows that the deposited weight fractions (%) is lower while gelatin contents exhibit higher, because the denser gelatin polymer chains would hinder the nanoparticles to grow. The highest content of the deposited magnetic nanoparticles could reach to 9.41% and its saturation magnetization (Ms) was 23.5 emu/g. In addition, the ferroscaffoleds displays high water contained and drug uptake (%) and potentially could be anticipated to apply in stimuli-responsive drug carriers and tissue engineering.