中空中孔洞氫氧基磷灰石奈米粒子的製備及細胞內藥物傳輸的應用

Synthesis of Hollow Mesoporous Hydroxyapatite Nanoparticles for Intracellular Drug Delivery

楊雅惠(Ya-Heui Yang)

指導教授 ： 吳嘉文

國立臺灣大學/工學院/化學工程學研究所/碩士(2011年)

https://doi.org/10.6342/NTU.2011.02570

摘要

本研究探討了中空中孔洞氫氧基磷灰石奈米粒子 (hm-HANPs) 的製備及其在細胞內藥物傳輸的應用。在合成材料的部分，藉由調控乙二醇的多寡、形成碳酸鈣核的反應時間、醋酸鈣和碳酸氫鈉水溶液的濃度、磷酸水溶液的濃度與醋酸水溶液的多寡，探討對合成中空中孔洞氫氧基磷灰石奈米粒子 (hm-HANPs) 的影響。實驗結果顯示最佳合成條件如下: 碳酸鈣前趨液與乙二醇的體積比是1:5、形成碳酸鈣核的反應時間是3小時、碳酸鈣前趨液是 0.3 M 醋酸鈣與 0.3 M 碳酸氫鈉水溶液、0.01 M 磷酸水溶液以及碳酸鈣前趨液與醋酸水溶液的體積比須超過1:3.125。利用此最佳合成條件，可製備出粒俓均勻 (400 x 600 nm) 且單一分布的中空中孔洞氫氧基磷灰石奈米粒子。在細胞內藥物傳遞的部分，選擇抗癌藥doxorubicin (DOX)裝載於hm-HANPs的內部。實驗結果顯示，相較於實心結構的氫氧基磷灰石奈米粒子，中空中孔洞氫氧基磷灰石奈米粒子有較高 (i.e., 五倍) 的藥物負載量。此外，hm-HANPs的中孔洞殼減慢DOX從中空結構內部釋放出來的速度，進而減緩釋放初期的突釋現象。在不同的酸鹼值影響下，hm-HANPs也表現出不同的釋放行為。同時，與單獨使用DOX相較下，DOX-loaded hm-HANPs的抗癌療效有明顯的提升。可得知，利用這種DOX-loaded hm-HANPs易受酸鹼值影響的特性，將有助於其應用於可調控的藥物傳遞系統。

關鍵字

氫氧基磷灰石 ； 中空 ； 奈米粒子 ； doxorubicin ； BT-20癌細胞 ； 藥物載體 ； 藥物傳遞

並列摘要

This study reports the synthesis and intracellular drug delivery of hollow mesoporous hydroxyapatite nanoparticles (hm-HANPs). For the synthesis part, the effects of several critical factors including the amount of ethylene glycol (EG), reaction time to form CaCO3 cores, concentrations of Ca(CH3COO)2(aq) and NaHCO3(aq), concentration of H3PO4(aq) and the amount of CH3COOH(aq) were investigated for synthesizing hollow mesoporous hydroxyapatite nanoparticles (hm-HANPs). We optimized the reaction conditions as follows: The ratio of CaCO3 precursor solution to EG was 1:5. Reaction time to form CaCO3 cores was 3hr. The CaCO3 precursor solution was 0.3 M Ca(CH3COO)2(aq):0.3 M NaHCO3(aq). The concentrations of H3PO4(aq) was 0.01 M. And the ratio of the CaCO3 precursor solution to CH3COOH(aq) was over 1:3.125. The monodispersed hm-HANPs with a defined particle size (400 x 600 nm) could be achieved. For the intracellular drug delivery part, doxorubicin (DOX) was used as an anticancer drug and loaded into hm-HANPs. We found that hm-HANP exhibited higher (i.e., five times) drug loading capacity than HANPs without hollow core. In addition, mesoporous shell of hm-HANPs slowed down the release of loaded DOX, reducing the burst release at the beginning. Our hm-HANPs also exhibited pH-responsive release behavior. Compared with free DOX, the anticancer efficacy of DOX-loaded hm-HANPs was greatly enhanced. This pH-sensitive property of DOX-loaded, hm-HANPs would be useful for controlled drug delivery system.

並列關鍵字

hydroxyapatite ； hollow ； nanoparticles ； doxorubicin ； BT-20 cancer cells ； drug carrier ； drug delivery

參考文獻

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