一種新穎雙性氧化矽-幾丁聚醣混成分子在葯物控制釋放之應用及此混成分子之磁性功能化研究

Abstract

在這一年的國科會計畫(NSC98-2113-M-009-004)，透過分子的設計與13C NMR 與29Si NMR 的鍵定，本實驗室已成功的合成出一種兩性的氧化矽-幾丁聚醣混成 分子(簡寫為S-CHC)(CHC 為一新型改質carboxyl-hexanoyl 幾丁聚醣)。在此二年期 的提案中，我們將更深入地研究此種新型混成分子與特定藥物分子間的作用，將 以疏水藥物(紫杉醇)與親水藥物(小紅莓)做為模型。此兩性混成分子的親水、疏 水端和藥物分子作用所產生的物理、化學行為將會深入探討。我們預期此兩性混 成分子會對藥物分子有不同程度的親合度，藉此親合力的誘引來捕抓藥物，改善 藥物包覆的效率，同時藉由分子間的控制來影響藥物釋放之動力學。。此混成分 子(控制組與包覆藥物組)對於正常細胞(上皮細胞)與癌細胞(肺癌，乳癌細胞)的細 胞相容性與標靶胞吞作用也是我們研究的重點之一。此外，在未來的研究方向 裡，我們亦企圖增加此混成分子的功能性，可能藉由化學改質在silanol 的部分 架接磁性物質(例如；氧化鐵)。此多功能的磁性添加、兩性S-CHC 混成分子可同 時結合磁控制藥物釋放，診斷和標靶，增加治療的效益。我們高度期望此silica-CHC 混成分子和磁添加的silica-CHC 混成分子可具新奇且之前未被探討的特性，而這 項研究工作應該會開出一條新的路徑，深入了解此一針對在臨床上重要藥物分子 的新混成系統，及其在生物醫學應用的潛力，將在化學物理和生物醫學的基礎 上，同時提供科學和技術的優勢。

With an advanced development of amphiphilic silica-CHC (abbrev. As S-CHC) hybrid molecule (where CHC is indicative of a newly-formed carboxyl-hexanoyl chitosan) which has been successfully synthesized in this lab in a recent 1-year NSC project (NSC-98-2113-M-009-004) through a molecular design and characterization with C- and Si- NMR spectra. In this 2-year proposal, we continue the work toward a deeper analysis in regard with the interaction of such a new hybrid molecule with specific drug molecules involved both hydrophobic drug (paclitaxel) and hydrophilic drug (doxorubin hydrochloride) as two model molecules. Both physical and chemical interactions of hydrophobic segments and hydrophilic segments interplaying between the new amphiphilic hybrid molecule and those drug molecules can be expected. We expect that both interactions may bring affinity of various strengths to impart drug-hybrid interaction, thus enhancing affinity-driven entrapment efficiency and in the meantime, molecularly regulate resulting release kinetics. It is also critical to learn the cytocompatibility and targeting endocytosis (Wei-Ling Tung, Shang-Hsiu Hu, and Dean-Mo Liu*, “Design and Synthesis of Functionalized Nanoparticles with Magnetically-remoted Drug Release Control and Enhanced Targeting Intracellular Delivery for Cancerous Cells”, Journal of Controlled release, in review 2009) of the new hybrid (control and with drug) toward both normal cells (epithelial cell line) and cancerous cells (A549 and MCF-7) through a targeting moiety anchorage. Beside, we also intend to enhance the functionality of the new hybrid molecule with a further chemical modification using magnetic lattice (i.e., Fe3O4) along the silanol group of the hybrid chain. A multifunctionality of the magnetic-doped amphiphilic S-CHC hybrid included magnetically-remoted control drug releasing, diagnosis, and targeting can be integrated simultaneously to strengthen therapeutic efficacy and strategy. It is highly anticipated that such a S-CHC and magnetic-doped S-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 systems toward clinically important drug molecules, associated with its potential biomedical applications.