表面修飾之中孔徑氫氧基磷灰石作為抗憂鬱症藥物載體之研究

Abstract

現今，憂鬱症對現代人而言已構成相當的威脅，而且它也是個不容輕忽的病症，至今尚未有任何方法可以防止憂鬱症的發生。因此，擁有一個值得信任的抗憂鬱症藥物就格外重要，尤其早期治療可有效預防憂鬱症惡化跟復發。 在本論文中，我們利用中孔徑氫氧基磷灰石的降解之特性作為傳輸抗憂鬱症藥物的長效載體。中孔徑的氫氧基磷灰石經過丙烯酸(Acrylic acid, AA)和亞麻油酸(Linoleic acid, LA)的表面改質後與抗憂鬱症藥物-奧氮平® (Olanzapine, OLZ)-結合，而此實驗在為期七週的體外(in vitro)已被證實有持續性的藥物釋放。最後，LDH測試可證實HAP-AA-LA-OLZ奈米粒子的毒性是相當低的，而WST-1測試則可證實HAP-AA-LA-OLZ奈米粒子對細胞不會造成任何影響。此論文是第一個用中孔徑的氫氧基磷灰石作為藥物載體之研究。

Depression is becoming a dangerous threat among us nowadays, and it is a major concern that cannot be neglected. Currently, there is no sure way to prevent depression. Hence, it is essential to have a reliable medication at earlier stages to prevent depression from worsening and reoccurrence of symptoms. In this thesis report, we propose the use of mesoporous hydroxapatite (HAP) nanoparticle as a long-lasting antidepressant drug carrier for its unique attribute in biodegradability. HAP nanoparticles synthesized are surface-modified by acrylic acid (AA) and linoleic acid (LA) for various purposes. The surface-modified HAP nanoparticles are then loaded with the latest generation of antidepressant, olanzapine (Zyprexa®, OLZ). The results have indicated a steady release of drug in in vitro experiments for a 7-week period. Lastly, the relative low cytotoxicity of HAP-AA-LA-OLZ nanoparticles is proven by LDH, and WST-1 shows there is no negative effect on cell viability and cell proliferation in in vitro studies. This study is the first to report the use of hydroxyapatite as a mesoporous nanoparticle drug carrier.