目的 優(yōu)化咖啡酸苯乙酯納米混懸劑的處方,并考察其體外抑制乳腺癌細胞作用。方法 以泊洛沙姆188、蜂膠作為載體,采用反溶劑沉淀法制備,通過星點設(shè)計-效應(yīng)面法優(yōu)化最佳制備工藝參數(shù),并考察咖啡酸苯乙酯納米混懸劑的穩(wěn)定性、載藥量、包封率以及凍干保護劑的篩選,同時考察對4T1乳腺癌細胞的生長抑制作用和細胞攝取情況。結(jié)果 咖啡酸苯乙酯納米混懸劑的最優(yōu)處方為蜂膠0.88 mg/mL、咖啡酸苯乙酯1.86 mg/mL、泊洛沙姆1881 mg/mL,制備得到咖啡酸苯乙酯納米混懸劑平均粒徑為150 nm左右,包封率98%以上,在各種生理介質(zhì)中都能夠穩(wěn)定存在; 0.5%的BSA對于咖啡酸苯乙酯納米混懸劑的凍干保護效果最好?？Х人岜揭阴ゼ{米混懸劑對4T1乳腺癌細胞的抑制作用與咖啡酸苯乙酯相比提高了2.95倍?？Х人岜揭阴ゼ{米混懸劑被細胞攝取后主要分布在細胞質(zhì)中,隨著給藥時間的增長,攝取也逐步提高。結(jié)論 所得咖啡酸苯乙酯納米混懸劑具有較高的包封率、載藥量,并顯著提高了咖啡酸苯乙酯對于4T1細胞的抑制作用。

Objective To optimize formulation of caffeic acid phenethyl ester nanosuspensions (CAPE-NPs) and evaluate its antitumor activity against breast cancer cell in vitro.Methods Poloxam 188 and propolis were used as carriers, and the formulation was prepares by antisolvent precipitation method. Preparation process parameters were optimized using Box-Behnken design- response surface method. The stability, drug loading capacity, and encapsulation efficiency of CAPE-NPs were investigated, and the lyophilization protective agent was screened. At the same time, the growth inhibitory effect and cellular uptake of 4T1 breast cancer cells of CAPENPs was evaluated by MTT assay in vitro.Results The optimal formulation included 0.88 mg/mL propolis, 1.86 mg/mL caffeic acid phenethyl ester, and 1 mg/mL P188. The mean particle size was about 150 nm, and the encapsulation rate was above 98%. CAPE-NPs could stably exist in various physiological media. 0.5% BSA could play a good protective role in the freeze drying process of CAPENPs. The inhibitory effect of CAPE-NPs against 4T1 breast cancer cells was 2.95 times higher than that of caffeic acid phenethyl ester. After being taken up by cells, it is mainly distributed in the cytoplasm, and the uptake of CAPE-NPs gradually increases with the increase of administration time.Conclusion CAPE-NPs has high encapsulation efficiency and drug loading, and can significantly improves the inhibitory effect of caffeic acid phenethyl ester against 4T1 cells.

R285

中國醫(yī)學科學院醫(yī)學與健康創(chuàng)新工程重大協(xié)同創(chuàng)新項目(2016-12M-1-012)