開發同時包覆油相/水相藥物之磁性藥物膠囊載體

Abstract

本研究計畫，主要是協助開發出一種高生物相容性且可以同時夾帶油相與水相藥物及可以精準操 控兩種藥物釋放之磁敏感奈米中空球藥物載體。此種中空載體的合成，只需要單一兩性高分子與氧化 鐵結合，當與油相氧化鐵混和乳化之後，會自組裝成水-油-水的奈米中空球結構。氧化鐵除了可以穩 定油相外層，也是提供載體磁性的媒介。此製程不需要其他乳化劑的幫助，也不需要透過溶劑的作用， 簡單的乳化步驟便可得到，此技術不同以往所發表過的雙乳化結構製作方法中，需要繁雜的聚合反應 及相分離方式、或利用混摻共聚物來穩定水相油相介面，也不須靠著堅硬的無機物或官能基團充當外 層來穩定結構。合成後的雙乳化中載體經過多次離心後，仍然可保持完整。而且藉由控制高分子的分 子量，便能夠控制載體的大小，從數十奈米至數百奈米均可得到。 由於載體具有水相內核及油相殼層，可以簡單的螯合各種藥物於核中或殼內，且由於穩固的殼 層，藥物自然漏藥的現象大幅降低。而當施加交流磁場時，氧化鐵受作用發熱，使高分子層結構開始 變化解，此時藥物快速釋出；當控制磁場開關交互進行時，可以控制藥物分段釋放。而產生的溫度也 可用於熱療。此外，具有超順磁性的氧化鐵使載體擁有核磁共振顯影的功能。而載體表面經過簡單的 修飾後，可對特定細胞有標靶的效果，在進行治療時可以有更好的效率。在藥物輸送以及生物醫學材 料上本材料均具有廣泛的應用，也將雙乳化中空球的結構賦予實際的可應用性與巨大的商機。

We designed a hollow nanocarrier with magnetic-sensitive and biocompatibility for drug-delivery, remote trigger, and MRimage in this work. The process to synthesize the hollow-structure drugcarrier is easier than other published techniques. In the past, methods about forming double-emulsion hollow spheres need complicated polymerization, phase separation, or the use of co-polymer and rigid inorganic to stabilize the W/O (O/W) interface and shell. This nanocarrier can be synthesized in only one surfactant water-soluble polymer incorporated with iron oxide nanoparticles to stabilize the oil/water and water/oil interface in the same time without the help of emulsifier and solvent. Because this kind of water-soluble polymer is an amphiphilic, after emulsifying with hydrophobic iron oxide nanoparticles, they will self-assemble into the water-oil-water hollow-structure sphere. Iron oxides not only stabilize the oil-phase shell, but also act as a magnetic media. This new technique provides a much easier method to synthesize the double-emulsion hollow spheres which are very stable and remain intact after several times centrifugation. Further, we can control the size of carriers from tens to hundreds of nanometer by changing the molecular weight of polymer. The nanocarriers possess hydrophilic core and hydrophobic shell, so molecules like drugs can be encapsulated into the core or shell depending on its character. Low release achieved because of the shell is stable. Under the magnetic field, iron oxides generate heat and the polymer structure change, causing the drug molecules diffuse out rapidly. In addition, it can also control step-like release behavior when a remote magnetic field is switched on and off. The nanocarriers can also act as MR imaging contrast agent. After modification, this hollow-structure nanocarrier can be used for targeted therapy. This invention provides a wide range of uses such as drug delivery and biomedical, and gives the practical application for double-emulsion hollow-structure spheres.