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聚(D,L-丙交酯)/聚乙二醇微/纳米纤维垫作为紫杉醇洗脱载体:纤维的制备和表征、体外药物释放、抗血管生成活性和肿瘤复发预防。

Poly(d,l-lactide)/polyethylene glycol micro/nanofiber mats as paclitaxel-eluting carriers: preparation and characterization of fibers, in vitro drug release, antiangiogenic activity and tumor recurrence prevention.

机构信息

Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic.

Department of Analytical Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43 Prague 2, Czech Republic.

出版信息

Mater Sci Eng C Mater Biol Appl. 2019 May;98:982-993. doi: 10.1016/j.msec.2019.01.046. Epub 2019 Jan 14.


DOI:10.1016/j.msec.2019.01.046
PMID:30813105
Abstract

Poly(d,l-lactide)/polyethylene glycol (PLA/PEG) micro/nanofibers loaded with paclitaxel (PTX, 10 wt%) were prepared by needless electrospinning technology, which allows large scale production for real medicinal practice. The fiber structure and properties were investigated by several methods including scanning electron microscopy, nitrogen adsorption/desorption isotherm measurements, differential scanning calorimetry, and X-ray diffraction measurements to examine their morphology (fiber diameter distribution, specific surface area, and total pore volume), composition, drug-loading efficiency, and physical state. An HPLC-UV method was optimized and validated to quantify in vitro PTX release into PBS. The results showed that the addition of PEG into PLA fibers promoted the release of higher amounts of hydrophobic PTX over prolonged time periods compared to fibers without PEG. An in vitro cell assay demonstrated the biocompatibility of PLA/PEG fibrous materials and showed significant cytotoxicity of PTX-loaded PLA/PEG fibers against a human fibrosarcoma HT1080 cell line. The chick chorioallantoic membrane assay proved that PTX-loaded fibers exhibited antiangiogenic activity, with a pronounced effect in the case of the PEG-containing fibers. In vivo evaluation of PTX-loaded PLA/PEG fibers in a human fibrosarcoma recurrence model showed statistically significant inhibition in tumor incidence and growth after primary tumor resection compared to other treatment groups.

摘要

载紫杉醇(PTX,10wt%)的聚(D,L-丙交酯)/聚乙二醇(PLA/PEG)微/纳米纤维通过无针电纺技术制备,该技术允许大规模生产,适用于实际的医学实践。通过几种方法研究了纤维的结构和性能,包括扫描电子显微镜、氮气吸附/解吸等温线测量、差示扫描量热法和 X 射线衍射测量,以检查其形态(纤维直径分布、比表面积和总孔体积)、组成、载药效率和物理状态。优化和验证了 HPLC-UV 方法,以定量测定 PBS 中 PTX 的体外释放。结果表明,与不含 PEG 的纤维相比,PEG 的加入促进了疏水性 PTX 的更高释放量和更长的释放时间。体外细胞试验证明 PLA/PEG 纤维材料具有生物相容性,并显示载药 PLA/PEG 纤维对人纤维肉瘤 HT1080 细胞系具有显著的细胞毒性。鸡胚绒毛尿囊膜试验证明载药纤维具有抗血管生成活性,含 PEG 的纤维具有明显的效果。在人纤维肉瘤复发模型中载药 PLA/PEG 纤维的体内评价表明,与其他治疗组相比,在原发性肿瘤切除后,肿瘤发生率和生长的统计学显著抑制。

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