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用于在人结肠直肠HT-29细胞中实现阿霉素局部释放的改性细菌纤维素支架

Modified bacterial cellulose scaffolds for localized doxorubicin release in human colorectal HT-29 cells.

作者信息

L Cacicedo Maximiliano, E León Ignacio, S Gonzalez Jimena, M Porto Luismar, A Alvarez Vera, Castro Guillermo R

机构信息

Nanobiomaterials Laboratory, Institute of Applied Biotechnology (CINDEFI, UNLP-CONICET-CCT La Plata), Department of Chemistry, School of Sciences, Universidad Nacional de La Plata, Calle 47 y115, CP 1900 La Plata, Argentina.

Chemical Inorganic Center (CEQUINOR, UNLP, CONICET), School of Sciences, Universidad Nacional de La Plata (UNLP), Calle 47 y 115, (1900) La Plata, Argentina.

出版信息

Colloids Surf B Biointerfaces. 2016 Apr 1;140:421-429. doi: 10.1016/j.colsurfb.2016.01.007. Epub 2016 Jan 11.

Abstract

Bacterial cellulose (BC) films modified by the in situ method with the addition of alginate (Alg) during the microbial cultivation of Gluconacetobacter hansenii under static conditions increased the loading of doxorubicin by at least three times. Biophysical analysis of BC-Alg films by scanning electron microscopy, thermogravimetry, X-ray diffraction and FTIR showed a highly homogeneous interpenetrated network scaffold without changes in the BC crystalline structure but with an increased amorphous phase. The main molecular interactions determined by FTIR between both biopolymers clearly suggest high compatibility. These results indicate that alginate plays a key role in the biophysical properties of the hybrid BC matrix. BC-Alg scaffold analysis by nitrogen adsorption isotherms revealed by the Brunauer-Emmett-Teller (BET) method an increase in surface area of about 84% and in pore volume of more than 200%. The Barrett-Joyner-Halenda (BJH) model also showed an increase of about 25% in the pore size compared to the BC film. Loading BC-Alg scaffolds with different amounts of doxorubicin decreased the cell viability of HT-29 human colorectal adenocarcinoma cell line compared to the free Dox from around 95-53% after 24h and from 63% to 37% after 48 h. Dox kinetic release from the BC-Alg nanocomposite displayed hyperbolic curves related to the different amounts of drug payload and was stable for at least 14 days. The results of the BC-Alg nanocomposites show a promissory potential for anticancer therapies of solid tumors.

摘要

在静态条件下,在汉逊醋杆菌微生物培养过程中通过原位法添加藻酸盐(Alg)对细菌纤维素(BC)膜进行改性,可使阿霉素的负载量增加至少三倍。通过扫描电子显微镜、热重分析、X射线衍射和傅里叶变换红外光谱对BC-Alg膜进行生物物理分析,结果表明其具有高度均匀的互穿网络支架,BC晶体结构未发生变化,但非晶相增加。傅里叶变换红外光谱确定的两种生物聚合物之间的主要分子相互作用清楚地表明了高相容性。这些结果表明,藻酸盐在杂化BC基质的生物物理性质中起关键作用。通过布鲁瑙尔-埃米特-特勒(BET)方法对BC-Alg支架进行氮吸附等温线分析,结果显示表面积增加约84%,孔体积增加超过200%。与BC膜相比,巴雷特-乔伊纳-哈伦达(BJH)模型还显示孔径增加约25%。与游离阿霉素相比,用不同量的阿霉素负载BC-Alg支架可降低HT-29人结肠直肠腺癌细胞系的细胞活力,24小时后从约95%降至53%,48小时后从63%降至37%。BC-Alg纳米复合材料中阿霉素的动力学释放显示出与不同药物负载量相关的双曲线,并且至少稳定14天。BC-Alg纳米复合材料的结果显示出在实体瘤抗癌治疗中的潜在应用前景。

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