Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India; Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
Colloids Surf B Biointerfaces. 2015 Jul 1;131:170-81. doi: 10.1016/j.colsurfb.2015.04.063. Epub 2015 May 7.
Since the turn of the 21st century, nanofiber based drug delivery systems have evolved drastically to attain controlled and sustained delivery of various bioactive molecules. In spite of such efforts, the tangible interface existing between the target cells and the drug molecules could not be narrowed down. This drawback has been overcome in this work by realizing nanofiber based scaffold for delivery of polymer-drug complexes rather than just the drug. In course with this, in the present study a differentially cross-linkable bPEI-PEO (branched-polyethylenimine-poly(ethylene oxide)) based nanofiber is fabricated for tunable delivery of bPEI-niclosamide complexes. Hydrophilic bPEI-niclosamide complexes are pre-synthesized and stabilized by crosslinking agent, which were then incorporated into bPEI-PEO nanofibers by electrospinning. The niclosamide loaded nanofibers by virtue of bPEI moieties presence were then cross-linked to different degrees which in turn altered bPEI-niclosamide release profile. The release kinetics of bPEI-niclosamide complexes from nanofibers was elucidated further by Korsmeyer-Peppas model. Apart from this, the versatile nature of bPEI-PEO nanofibers was also validated for different drug loading concentration and extent of crosslinking. The fibers antitumor efficacy was then assessed against A549 (Non-small cell lung cancer cells) and U-87 MG (glioblastoma cells) at two different time points (at 48h and 96h) in order to realize the importance of release profile in manifestation of different therapeutic outcomes. Thus, this work endows niclosamide a new life for anticancer application which has remained elusive till date due to its hydrophobic nature.
自 21 世纪初以来，基于纳米纤维的药物输送系统已经有了很大的发展，以实现各种生物活性分子的控制和持续输送。尽管有这样的努力，但目标细胞与药物分子之间存在的有形界面仍然无法缩小。在这项工作中，通过实现基于纳米纤维的聚合物-药物复合物的输送支架，而不仅仅是药物，克服了这一缺陷。在这个过程中，在目前的研究中，制备了一种可区分交联的 bPEI-PEO（支化聚乙基亚胺-聚（环氧乙烷））基纳米纤维，用于调节 bPEI-氯硝柳胺复合物的输送。亲水性 bPEI-氯硝柳胺复合物通过交联剂预先合成并稳定，然后通过静电纺丝将其掺入 bPEI-PEO 纳米纤维中。然后，通过 bPEI 部分的存在将负载有氯硝柳胺的纳米纤维交联到不同程度，从而改变 bPEI-氯硝柳胺的释放曲线。通过 Korsmeyer-Peppas 模型进一步阐明了 bPEI-氯硝柳胺复合物从纳米纤维中的释放动力学。除此之外，还验证了 bPEI-PEO 纳米纤维的多功能性，用于不同的药物负载浓度和交联程度。然后，在两个不同的时间点（48h 和 96h），针对 A549（非小细胞肺癌细胞）和 U-87 MG（神经胶质瘤细胞）评估纤维的抗肿瘤功效，以实现释放曲线在不同治疗结果表现中的重要性。因此，这项工作赋予了氯硝柳胺新的抗癌应用，由于其疏水性，这一应用至今仍难以实现。
