磁性單晶奈米膠囊結構的製備、材料性質與藥物釋放研究

Abstract

傳統的藥物載體在人體中並未真正達到完善地控制釋放的目的，因為其藥物釋放僅 是隨著藥物載體的特性與所在的環境變化而產生，此外，傳統之藥物載體容易在輸送的 過程中損失藥物，無法良好夾帶藥物。因此，本計畫的主要研究的創新，就是發展出一 種磁性單晶膠囊結構，可將藥物夾帶於膠囊體中，大幅降低藥物損失，並可利用奈米磁 粒子載體來感應電磁場的變化，控制藥物的釋放或關閉，形成智慧型奈米複合生醫材料 結構。故本計畫將針對此具有磁敏感性之單晶型態的殼結構及奈米膠囊藥物載體的藥物 釋放及操控，以三年來完成這方面相關重要的研究，其主要研究的內容可包括(i)奈米單 晶膠囊藥物載體設計與製程研究，使其核具有藥物攜帶特性，而奈米膠囊藥物載體則具 有生物相容性與磁敏感特性。(ii) 研究及瞭解奈米膠囊之單晶氧化鐵”殼”結構的成長機 制，並應用此機制去探討與發展其他磁性材料單晶膠囊的製程。(iii) 利用晶體成長操控 達到奈米膠囊藥物載體的可操控特性，如殼厚度的操控與核組成、藥物攜帶與尺度的變 化。並使得奈米膠囊藥物載體達藥物”零釋放”特性。(iv) 探討奈米單晶膠囊在不同頻率 及磁場大小與作用時間下，所造成單晶結構的形變(v) 利用外部磁場精準操控奈米膠囊 藥物載體的藥物釋放特性。(vi) 不同磁性材料置換對於奈米膠囊藥物載體的影響性研 究，如磁特性與磁場下藥物釋放的操控性。(vii)不同磁特性奈米膠囊藥物載體之多階段 釋放藥物特性研究。(viii) 評估外加磁場對於奈米單晶膠囊藥物載體標靶細胞的影響及 特性。(ix)利用生物標靶分子(targeting ligands)接枝在單晶奈米膠囊藥物載體的表面上， 使載體具有標靶性的功能研究。(x) 不同磁特性奈米膠囊藥物載體於磁振造影(MRI)的特 性分析。以期可以找到藥物釋放、奈米單晶殼厚度與磁敏感特性之間的關連性，發展出 一套物理模式。應用此功能性單晶奈米膠囊藥物載體，達到診斷、標靶與磁場操控藥物 輸送及定位治療的效果。

Controlled release of therapeutic drugs for medication has been extensively investigated for decades. However, in tradition, the drug molecules encapsulated into the host tend to be released drug during circulation in body can be detected via diffusion of drug in most of the current existing drug delivery systems. Since magnetic stimulation is an action-at-distance force (non-contact force), the drug-carriers can be developed into smart magnetic-sensitive nano-capsules. Therefore, in the three-year’s research proposal, a novel core-shell nanocapsule with a unique shell structure made of single-crystalline highly-biocompatible ferrites will be proposed to explore (i) Control growth of the single-crystal ferrite shell nanostructure through an aqueous- or solvent-mediated mechanism. (ii) Drug release kinetics of the nanocapsule with single-crystal magnetic shell in terms of the thickness of magnetic single-crystal shell of different size nanocapsules under the stimulus of different magnetic field with different frequencies. (iii)The structure transformation and morphology of magnetic-induced structural deformation of the single-crystal shell in the magnetic nanocapsules under the application of different magnetic field will be further analyzed by HRTEM and Beam-line. (iv) Some physical characterizations would be investigated using X-ray diffraction (XRD), Raman spectrometry, X-ray photoelectron spectroscope (XPS), and SQUID. (v) How the drug- loading and “zero-release” can be well regulated by controlled release (vi) How to apply the formation mechanism of single-crystal shell to other ferrites to develop other magnetic nanocapsules with single-crystal shell and further study their magnetic-sensitive properties and controlled drug release under applying a magnetic field. (vii) Multiple-stages controlled drug release behavior and kinetics by incorporating different nanocapsules with different magnetic-sensitive properties. (viii) Some biocompatibility test, including cytotoxicity and biocompatible test on the magnetic nanocapsule. (ix) Surface modification of the ferrite shell with antibody or ligands that allows a targeting ability (cell recognition) of the resulting nanocapsules to be deliverable on a cell-specific base in vivo. (x).Enhanced MRI imagining sensitivity and drug-release of the nanocapsules under exposure to magnetic fields.