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负载灵菌红素的电纺纳米纤维支架用于三阴性乳腺癌的局部治疗。

Prodigiosin-loaded electrospun nanofibers scaffold for localized treatment of triple negative breast cancer.

作者信息

Akpan U M, Pellegrini M, Obayemi J D, Ezenwafor T, Browl D, Ani C J, Yiporo D, Salifu A, Dozie-Nwachukwu S, Odusanya S, Freeman J, Soboyejo W O

机构信息

Department of Materials Science and Engineering, African University of Science and Technology, Federal Capital Territory, Abuja, Nigeria.

Department of Biomedical Engineering, Rutgers University, New Brunswick, NJ. USA.

出版信息

Mater Sci Eng C Mater Biol Appl. 2020 Sep;114:110976. doi: 10.1016/j.msec.2020.110976. Epub 2020 Apr 18.

Abstract

Hybrid composite nanofibers, with the potential to enhance cell adhesion while improving sustained drug release profiles, were fabricated by the blend electrospinning of poly(d,l-lactic-co-glycolic acid) (PLGA), gelatin, pluronic F127 and prodigiosin (PG). Scanning Electron Microscopy (SEM) images of the nanofibers revealed diameters of 1.031 ± 0.851 μm and 1.349 ± 1.264 μm, corresponding to PLGA/Ge-PG and PLGA/Ge-F127/Ge, respectively. The Young's moduli were also determined to be 1.446 ± 0.496 kPa and 1.290 ± 0.617 kPa, while the ultimate tensile strengths were 0.440 ± 0.117 kPa and 0.185 ± 0.480 kPa for PLGA/Ge-PG and PLGA/Ge-F127/Ge, respectively. In-vitro drug release profiles showed initial (burst) release for a period of 1 h to be 26.000 ± 0.004% and 16.000 ± 0.015% for PLGA/Ge and PLGA/Ge-F127 nanofibers, respectively. This was followed by 12 h of sustained release, and subsequent slow sustained release of PG from the composite nanofibers. The cumulative release of PG (for three days) was determined to be 82.0 ± 0.1% for PLGA/Ge and 49.7 ± 0.1% for PLGA/Ge-F127 nanofibers. The release exponents (n) show that both nanofibers exhibit diffusion-controlled release by non-Fickian (zeroth order) and quasi-Fickian diffusion in the initial and sustained release regimes, respectively. The suitability of the composite nanofibers for supporting cell proliferation and viability, as well as improving sustained release of the drug were explored. The in-vitro effects of cancer drug (PG) release were also studied on breast cancer cell lines (MCF-7 and MDA-MB-231 cells). The implications of the results are discussed for the potential applications of drug-nanofiber scaffolds as capsules for localized delivery of chemotherapeutic drugs for the treatment of triple negative breast cancer.

摘要

通过聚(d,l-乳酸-乙醇酸共聚物)(PLGA)、明胶、普朗尼克F127和灵菌红素(PG)的共混电纺丝制备了具有增强细胞粘附力同时改善药物持续释放特性潜力的混合复合纳米纤维。纳米纤维的扫描电子显微镜(SEM)图像显示,直径分别为1.031±0.851μm和1.349±1.264μm,分别对应于PLGA/Ge-PG和PLGA/Ge-F127/Ge。PLGA/Ge-PG和PLGA/Ge-F127/Ge的杨氏模量分别测定为1.446±0.496kPa和1.290±0.617kPa,而极限拉伸强度分别为0.440±0.117kPa和0.185±0.480kPa。体外药物释放曲线显示,PLGA/Ge和PLGA/Ge-F127纳米纤维在1小时的初始(突释)释放分别为26.000±0.004%和16.000±0.015%。随后是12小时的持续释放,以及PG从复合纳米纤维中的后续缓慢持续释放。PLGA/Ge和PLGA/Ge-F127纳米纤维中PG的累积释放(三天)分别测定为82.0±0.1%和49.7±0.1%。释放指数(n)表明,两种纳米纤维在初始和持续释放阶段分别通过非菲克(零级)和准菲克扩散表现出扩散控制释放。研究了复合纳米纤维对支持细胞增殖和活力以及改善药物持续释放的适用性。还研究了癌症药物(PG)释放对乳腺癌细胞系(MCF-7和MDA-MB-231细胞)的体外影响。讨论了结果对于药物纳米纤维支架作为用于局部递送化疗药物治疗三阴性乳腺癌的胶囊的潜在应用的意义。

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