兩性共聚物微胞做為乘載順鉑抗癌藥物之載體

Chondroitin sulfate-g-poly(ε-caprolactone) micelles as a delivery system for cisplatin

何佳靜(Chia-Ching Ho)

指導教授 ： 王麗芳

高雄醫學大學/生命科學院/醫藥暨應用化學系碩士在職專班/碩士(2016年)

摘要

本研究使用疏水性聚己內酯(poly-ε-caprolactone, PCL)接枝到親水性硫酸化軟骨素(chondroitin sulfate, CS)上，形成一個兩性共聚物CS-g-PCL (CP)，CP在水中可自組裝形成微胞，內層疏水之聚己內酯，作為核心，而親水性之硫酸化軟骨素為外殼，提供保護及維持長期循環，增加其穩定性。而微胞外層之硫酸化軟骨素上的羧基(carboxylic groups)有利於和含鉑抗癌藥物順鉑(cisplatin, CDDP)透過化學鍵結形成polymer-metal complex，進而達到乘載藥物之作用。
合成反應上，利用不同莫耳比例之CDDP及硝酸銀(silver nitrate, AgNO3)製備出[PtCl(NH3)2NO3]+及[Pt(NH3)2(NO3)2]2+，再分別和載體微胞反應製備成載藥的微胞。檢測方面，利用鄰苯二胺(OPDA)比色法以紫外光-可見光(UV-vis)光譜儀測定載體微胞中CDDP含量，透過穿透式電子顯微鏡(TEM)觀測載體微胞載藥前後之型態及利用動態光散射分析儀(DLS)測定其水合粒徑大小。
在藥物釋放實驗上，觀察探討載藥微胞於不同氯離子環境下的藥物釋放的狀況。在體外細胞實驗中，Free CDDP對非小細胞肺癌細胞 CRL-5802具較佳之毒殺成效，在細胞餵藥48小時的測試上，載藥微胞和Free CDDP對CRL-5802之毒殺效果具有相當的能力。

關鍵字

聚己內酯 ； 硫酸化軟骨素 ； 順鉑

並列摘要

In this study, we used an amphiphilic copolymer micelles which are synthesized by grafting a hydrophobic polymer, poly(ε-caprolactone) (PCL) onto a hydrophilic polymer, chondroitin sulfate (CS). These copolymers self-assemble into core-shell micelles in an aqueous condition. The inner core of PCL and the outer shell of CS endow micelles for drug protection as well as good stability in bloodstream. The carboxylic groups of CS were used to coordinate with an anti-cancer drug, cisplatin (CDDP). These polymer-metal complexes could be used for cancer therapy.
[PtCl(NH3)2NO3]+and [Pt(NH3)2(NO3)2]2+ were prepared using different molar ratios of CDDP and silver nitrate and further complexed with the copolymer micelles. The CDDP content of drug-loaded micelles was measured by o-phenylenediamine (OPDA) colorimetry and ultraviolet-visible spectrophotometry (UV-Vis). We used dynamic light scattering (DLS) and transmission electron microscope (TEM) to observe the hydrodynamic diameters and morphologies of the micelles before and after encapsulation of CDDP.
Drug release profiles of CDDP-loaded micelles in PBS with different ionic strengths were carried out. For in vitro test, the CDDP-loaded micelles show similar cytotoxicity to free CDDP against CRL-5802 cells for 48 hours incubation.

並列關鍵字

poly-ε-caprolactone ； chondroitin sulfate ； cisplatin

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