标题: 设计与合成磁酸硷敏感型含钙磷酸盐包覆双性明胶奈米药物载体于癌症治疗之研究
Design and Synthesis of Magnetically pH-Sensitive Amphiphilic Gelatin@Calcium Phosphate Nanocarries for Cancer Therapy
作者: 李伟铭
Li, Wei-Ming
陈三元
Chen, San-Yuan
材料科学与工程学系所
关键字: 磷酸钙;酸硷敏感性;控制释放;双性明胶;Calcium phosphate;pH-sensitivity;Drug release;amphiphilic gelatin
公开日期: 2013
摘要: 本研究为设计与合成一种多功能且能包覆不同药性之奈米药物载体,其载体的主体为一种由亲/疏水双性改质之明胶经自我组装的方式,形成奈米粒子来作为药物载体之核心结构。并可藉由不同实验参数的调控如疏水性分子的种类及不同亲水性之官能基,进而改变其不同接枝率和微胞浓度。双性明胶分子,可在溶于水溶液后,自我组装形成奈米级尺寸的奈米球结构。此结构能够使其拥有更多的空间来装载药物,大量提升疏水性药物包覆率。并可藉由不同亲疏水性的变化来做为不同速度的释放之载体。双性明胶利用自组装的特性使其得以在不破坏药物本身的活性下完成药物的包覆工作,得以保存最佳药物活性。双性明胶奈米球结构拥有能够有效包覆各种药物分子、如抗癌药物等。此外,双性明胶本身具备的负电荷可与正电荷之离子有电荷吸引的作用,因此可利用此方式与一些生物矿物结合,设计与制备出一种具酸硷敏感及磁性之新型核-壳奈米药物载体,利用乳化步骤包覆疏水性药物及磁性奈米粒子,制备出磁性双性明胶奈米球体之药物载体,再者,将氧化铁@双性明胶奈米球体作为核心,并利用共沉法的方式,同时在形成氢氧基磷灰石壳层的过程中,同时加入亲水性药物分子,将亲水性药物分子完美的包覆于壳层当中,此包覆药物的方式可以氧化铁/双性明胶@氢氧基磷灰石载体同时包覆两种不同性质之药物分子,形成双药载体。此时由于药物包覆在不同位置,而核心与壳层之药物释放机制不同,因此可以造成不同阶段药物释放行为。此外,可以利用特殊的磷酸根分子键结在氢氧基磷灰石的表面提供官能基,进一步再载体表面修饰上抗体,使载体本身具有标靶辨别,并提高癌症的治愈疗效。而且药物的释放行为,则因为氢氧基磷灰石壳层会在酸性溶液下溶解,而且若外在环境酸性程度越高则药物释放越快速,因此达到有效控制药物分布。
此药物奈米载体之材料特性与药物的结合特性,除了具有控制释放药物可利用磁性氧化铁粒子来当作磁场引导,并同步监测药物载体的位置情形,磁振显影(MRI)的显影剂用于侦测肿瘤细胞位置,可将大量的抗癌药物累积及控制药物的释放,以达到肿瘤治疗的效果。
The investigation discloses that amphiphilic gelatin derivatives modified by hydrophobic functional groups can be formed nanoparticles in aqueous solutions by self-assembly. Control of synthetic parameters included the type of hydrophilic and hydrophobic functional groups, the ratio of the degree of hydrophobic substitutions and critical aggregation concentration (CAC). This amphiphilic gelatin nanoparticle can be used as a drug carrier for various therapeutic purposes. The positively-charged ions attract toward carboxyl group of amphiphilic gelatin by electrostatic interactions to permit the deposition of biomineral on the surface of nanoparticles. Therefore, An amphiphilic gelatin-assembled iron oxide/calcium phosphate core-shell (AGIO@CaP) nanoparticle were developed for co-delivery of anti-cancer drug Camptothecin (CPT) and doxorubicin(DOX) where the hydrophobic agent (CPT) was encapsulated via emulsion with an amphiphilic gelatin core, and the hydrophilic drug (DOX) was encapsulated through precipitation on a CaP shell. Release studies from core/shell carriers showed the possibility of achieving sequential release of more than one type of drug. In addition, we proposed the surfactant-free method to link targeting ligand (Herceptin) on AGIO@CaP nanoparticles based on the affinity of Amifostine binding calcium phosphate. This strategy with the simultaneous formation of CaP-DOX nanostructure provided high biocompatibility and a highly pH-sensitive control when the AGIO@CaP nanoparticles were subjected to acidic environment such as cancer tissue or subcellular endosome. Furthermore, the AGIO@CaP nanoparticles combining advantages of magnetic nanoparticles and calcium phosphate can be optimally tuned to realize a multifunctional nanodevice with integrated modalities including drug delivery, environmentally-responsive intracellular release and MR imaging.
URI: http://140.113.39.130/cdrfb3/record/nctu/#GT079718821
http://hdl.handle.net/11536/74027
显示于类别:Thesis