二甲雙胍(Metformin, met)作為治療第二型糖尿病之藥物，近年研究指出具有協助抑制癌症之功效。厚朴酚(Magnolol, mag)為天然之中草藥萃取物，已知能誘導胃癌細胞、口腔癌鱗狀上皮細胞、肺癌細胞等多種癌症凋亡，但magnolol不易懸浮與分散性不佳之問題，限制其臨床應用性。為了改善magnolol之不易懸浮與分散性不佳之問題，本研究第一階段以PLGA作為magnolol之載體材料，製備微米顆粒(Mag-PLGA MPs)或奈米顆粒(Mag-PLGA NPs) ，透過MTT assay量測細胞存活率及caspase-3 ELISA kit分析細胞凋亡之程度，評估magnolol載體抑制人類牙齦上皮癌細胞株(OECM-1)之效果，並探討添加metformin對提升magnolol載體抑制OECM-1之影響。其次，以傳統雙重乳化法包覆親水性藥物metformin之效率極低，因此本研究第二階段嘗試以改良的雙重乳化法並調整不同之參數製備BSA-PLGA核殼微米顆粒(Core-shell microparticles)，藉此提升親水性藥物metformin包埋效率。
研究結果顯示，mag-PLGA NPs對於抑制OECM-1之能力較mag-PLGA MPs佳。且magnolol載體添加metformin之合併療法對降低OECM-1存活率可達到加成之作用。另一方面，包覆metformin之BSA-PLGA核殼微米顆粒其包埋效率與一般雙重乳化之顆粒相比，最多可達88.9%的提升。由結果顯示，magnolol及metformin之合併療法及核殼包埋親水性metformin對於口腔癌之治療是具有潛力的。

Magnolol, a kind of traditional herbal medicines extract from the bark of the Magnolia, is known to induce cancer cell apoptosis, such as, gastric adenocarcinoma, lung cancer cell and oral squamous cell carinoma. Metformin is a common used first line oral drug for type two diabetes, it is recently been reported to inhibit cancer. In the present study, in order to improve the poor suspension property and low aqueous solubility of magnolol, we prepared the magnolol loaded micro or nano particles by using PLGA as drug carrier, and then investigated the antitumor effect of magnolol drug carrier with or without metformin on oral epidermoid carcinoma cells (OECM-1). MTT assay was performed to quantify cell viability, on the other hand, TUNEL assay and caspase-3 ELISA kit were used to evaluate the apoptosis of OECM-1. Further, we prepared and optimized the core-shell microparticles comprising of a hydrophilic core of BSA surrounded by hydrophobic shell of PLGA to improve the encapsulation efficiency(EE%) of hydrophilic drug metformin.
The result showed that the inhibitory effect to OECM-1 of mag-PLGA NPs is better than mag-PLGA MPs. And reduction of OECM-1 viability can reach additive manner when combinatorial treated with magnolol drug carrier and metformin. On the other hand, the EE% of BSA-PLGA microparticle can reach 88.9% higher than normal double emulsion particles. Combined treatment with magnolol drug carrier and metformin may induce programmed cell death of OECM-1; Core-shell microparticle can improve the encapsulation of metformin. These findings reveal a potential therapeutic strategy of oral cancer.

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