以無機分子改質雙性機丁聚糖之自組裝混成複合材料及其生醫特性之研究

Abstract

幾丁聚醣(chitosan)為直鏈多糖體，是廣泛應用在醫學、藥學、化學分離、 環境工程等領域的天然高分子；幾丁聚醣具備生物相容性、生物可降解性、 無毒等性質，但是他難溶於中性溶劑，因此限制了其發展潛力。隨著合成 化學的進步，將有機官能基作疏水性改質已有效合成兩性衍生物，也常運 用作藥物載體、組織工程的支架等，現有許多研究在幾丁聚醣中加入無機 物，也致力發展有別於一般合成化學、材料化學、膠體化學、醫學、生物 科技等想法的創新思維。因此，利用有機無機複合物增加材料效能和特殊 性質也更顯重要。本實驗室在幾丁聚醣的骨架上利用親水性羧甲基酸 (carboxymethyl)和疏水性己醯基(hexanoyl)作幾丁聚醣的雙配位基改質，成 功合成出兩性幾丁聚醣，稱作CHC。CHC 可透過自組裝形成奈米顆粒或是 中空的奈米微胞，也可控制其尺寸和疏水程度。藉由控制CHC 的化學親和 力，可以調控包覆不同性質的藥物，以用做特殊醫療效果。另外，越來越 多的技術和研究截取無機配位基的優點，製備出多功能複合材料，這也是 此次計畫的中心思想。因此，接下來我們將進一步用無機配位基，如矽烷、 氧化鐵做分子內改質。值得一提的本實驗室已經合成出新的無機兩性CHC 複合物，且初步觀察到次奈米的形貌結構，我們可以樂觀地預期無機CHC 複合物具前瞻性的應用價值，且本研究計畫將深入探討此複合材料的化 學、物理、生醫特性並提供一個有效可行的合成方法。

Chitosan, a linear polysaccharide, has been well-known as a natural polymer for numerous applications from medicine, pharmaceutics, chemical separation, to environmental engineering. However, its poor solvency in neutral media and solvents limited its potential applications, even though it has exhibited biocompatibility, non-toxicity, and biodegradability. With the advancement of synthetic chemistry, hydrophobic modification with organic moieties has been employed to form amphiphilic counterpart and has been received great attentions, as for instance, drug carrier and scaffold for tissue engineering. Incorporation of inorganic component into chitosan molecule has recently been studied and has received increasingly attentions over the disciplines from synthetic chemistry, materials chemistry, colloidal science, medicine, and biotechnology, since it has recognized to integrate merits from inorganic and organic counterparts of the resulting hybrids, to further boost desirable properties with enhanced performance. Recently, a dual-ligand modification using hydrophilic carboxymethyl and hydrophobic hexanoyl pedants along the backbone of native chitosan, has been successfully synthesized in our lab and has giving a novel amphiphilc chitosan, termed as CHC, capable of self-assembling from dense nanoparticle to hollow nanocapsules with controllable size and hydrophobicity. They also showed a diverse ability for encapsulating therapeutic agents of various chemical affinity. However, it is more technically desirable and scientifically sound by taking the advantages of inorganic moieties with additional functionalities to the resulting hybrid, and this turns out to be the central issue of this research proposal, where we intend to further move this CHC molecule a step ahead by intramolecular modification with inorganic ligands, such as silanes and iron oxide, and according to our recent preliminary observation, a new class of amphiphilic inorganic-bearing CHC hybrid molecule with unprecedentedly sub-nano morphological structure can be obtained. It is highly anticipated that such an inorganic-bearing CHC molecular hybrid should exhibit new properties that may not be explored before and this research work should pave a new avenue to provide both scientific and technical advantages based on an in-depth understanding the chemical, physical, and biomedical fundamentals of this new hybrid system, associated with its potential (bio)technical applications.