阿霉素果胶纳米粒的制备及其体外抗肿瘤活性

Preparation and anti-tumor activity of doxorubicin-loading pectin nanoparticle in vitro

考察阿霉素果胶纳米粒（Doxorubicin-loading Pectin Nanopaticle，DOX-PEC-NP）的制备工艺及其体外抗癌作用．采用微乳法制备果胶纳米粒（Pectin Nanopaticle，PEC-NP），吸附载药制备载阿霉素果胶纳米粒，并用FT-IR、DSC与X线衍射法对纳米粒的成型与载药机理进行探讨．采用溴化四唑蓝比色法（MTT法）、流式细胞仪及激光共聚焦显微镜评价DOX-PEC-NP对Hela、MCF-7、HepG23种癌细胞株的体外抗肿瘤活性．所制备的PEC-NP通过静电相互作用成型并吸附阿霉素载药．DOX-PEC-NP外观圆整，平均粒径为（353.66±2.86）nm，电位为（-20.17±0.67）mV，包封率为90.63％，载药量为17.18％．不同质量浓度的DOX-PEC-NP（阿霉素终质量浓度：0.25、0.50、1.0、2.0、4.0μg/mL）分别作用于Hela细胞、MCF-7细胞、HepG2细胞24、48、72 h后，相比于阿霉素原料药，抑制率升高18.19％～27.14％，均具有显著性差异（P＜0.05）．流式细胞仪与激光共聚焦显微镜显示，DOX-PEC-NP更容易被肿瘤细胞摄取，发挥药效．阿霉素果胶纳米粒起效快，具有一定靶向作用，有望减少药物用量、降低毒副作用．

Theaimofthisstudywastoinvestigatethepreparationofdoxorubicin-loadingpectinnano-paticle （DOX-PEC-NP）and its anti-tumor activity in vitro.The pectin nanopaticle （PEC-NP）was pre-pared by microemulsification method,and DOX was adsorbed to PEC-NP for drug loading.The formation and drug loading mechanism of PEC-NP was discussed by using FTIR,DSC and X-ray powder diffrac-tion.The anti-tumor activity of DOX-PEC-NP was evaluated in Hela,MCF-7,HepG2 cells by 3-（4,5-Dimethylthiazol-2-yl）-2,5- Diphenyltetrazolium Bromide （MTT）colorimetry,flow cytometry and laser scanning confocal microscope.The electrostatic interaction accounted for the formation and drug loading of PEC-NP.The DOX-PEC-NP was spherical nanoparticle with an average size and zeta potential about （353.66 ±2.86）nm and （-20.1 7 ±0.67）mV,respectively.The entrapment efficiency （EE%）and drug loading rate of DOX-PEC-NP was 90.63% and 1 7.1 8%,respectively.The DOX-PEC-NP showed higher inhibitory rate than DOX in different concentrations （final concentration of DOX：0.25,0.50, 1.0,2.0,4.0 μg/mL）after 24,48,and 72 h incubation with all of the three cell lines,respectively.＆amp;nbsp;The inhibitory rate increased about 1 8.1 9%~27.1 4% and showed significant difference （P＆lt;0.05 ）. An easier uptake in cancer cells of DOX-PEC-NP was observed by flow cytometry and laser scanning con-focal microscope,which promoted the activity of drug.The DOX-PEC-NP played a fast action and dem-onstrated tumor cell targeting to a certain extent,which provided the possibility to reduce both dosage and toxicity.