分子疊層堆積於自組裝幾丁聚醣奈米載體應用於抗癌藥物釋放之研究

Abstract

現今藥物並非都能直接投入人體內，許多藥物具有溶解度、毒性、不穩定、易被分解等等的問題存在，因此，藥物載體便是為了解決此問題而開發出來。為了能將藥物運送至所需位置，各種材料、功用的載體應運而生。本實驗室在前幾年已成功研發出具有生物相容性之兩性幾丁聚醣(CHC)，並且基於CHC本身具有疏水端及親水端，以成功包覆藥物在此結構內部。為了能更有效降低外在環境對藥物之破壞及延長藥物釋放的時間，基於先前研究出CHC表面帶有電荷，我們合理地認為可利用物理吸附原理在CHC表面覆蓋上一層磺酸鈉聚苯乙烯(PSS) ，來降低藥物漏藥量及外在環境對藥物之破壞，延長釋放時間。在初步Size、Zeta potential 及SEM數據探討下，我們認為此概念具有極大可行性。因此，本計畫將以先前開發之CHC為藥物載體，並在外層覆蓋PSS，預期發展出layer by layer之結構，以開發長期、低漏藥之油溶性抗癌藥物載體為主要目標。在一年期的計畫，我們將更深入研究CHC@PSS之材料特性及結構並且以(S)-(+)-Camptothecin (CPT)疏水性藥物作為模型，之後進行細胞實驗，確保其生物相容性與實用性，以期未來能商品化，成為實用之藥物載體。

Bioavailability of drugs has been a well-known hurdle, due to solubility, toxicity, instability, leakage, dose insufficiency, etc., that restricts considerably the use of the drug with maximal therapeutic efficacy in human society. This is the major driving force for the development of micro-to-nano carriers toward improved bioavailability and to the ultimate goal: cellular-based nanotherapeutic strategy. Drug carriers enrich the efficacy by not only therapeutics, but also included a number of biofunctionalities such as targeting, imaging, diagnosis, etc., making a multi-purposed medication technically feasible. IN this proposal, we intend to employ an advanced development of amphiphilic carboxymethyl-hexanoyl chitosan (abbrev. as CHC) molecule that has been successfully synthesized in this lab in recent years, showing excellent cytocompatibility and capable of self-assembling into nanocapsule as a result of hydrophobic interaction. However, a sustain release with precisely controlled release profile and free-of-leakage are more critical to promote such carrier toward commercials, even from the earlier phase in circulation, on this basis, we intend to apply a layer-by-layer (LbL) deposition of anionic poly(sodium 4-styrene sulfonate) (abbrev. as PSS) on the surface of the cationic CHC by neutralization reaction. This LbL idea has preliminarily proved in our very earlier-stage investigation and we expect to develop a LbL molecular structure that regulates well the final drug carrier for long-term sustain drug release (with free of burst and leakage-free formulation). In this 1-year proposal, we continue the work toward deeper investigation of this design from the viewpoint of molecular interaction and nanochemistry to gain better understanding of the underlying mechanism of molecular-regulated release kinetics. It is also critical to understand the cytocompatibility and efficacy of a medicine to kill cancerous cell in vivo, before a successful commercials can be granted in the future.