School of Biological Sciences, Illawarra Health and Medical Research Institute, Centre for Medical and Molecular Bioscience, University of Wollongong, NSW, Australia.
ARC Centre of Excellence for Electromaterials Science, AIIM Facility, University of Wollongong, NSW, Australia.
Pancreatology. 2017 Sep-Oct;17(5):795-804. doi: 10.1016/j.pan.2017.06.001. Epub 2017 Jun 3.
BACKGROUND/OBJECTIVES: There has been minimal improvement in the prognosis of pancreatic cancer cases in the past 3 decades highlighting the crucial need for more effective therapeutic approaches. A drug delivery system capable of locally delivering high concentrations of chemotherapeutics directly at the site of the tumor is clearly required. The aim of this study was to fabricate and characterize the biophysical properties of gemcitabine-eluting wet-spun polymeric fibers for localized drug delivery applications.
METHODS/RESULTS: Fibers spun from alginate or chitosan solutions with or without the anticancer drug gemcitabine had a uniform surface area, were internally homogeneous and ranged from 50-120 μm in diameter. Drug encapsulation ranged from 13-52%, depending on the type and concentration of polymer used. Gemcitabine displayed first-order release kinetics where 64-82% of the loaded drug was rapidly released within the first 10 h followed by a sustained release over the next 134 h. A time dependent inhibition of ex vivo tumor spheroid growth and cell viability was observed after incubation with gemcitabine-loaded fibers but not control fibers.
With further development these studies could lead to the manufacture of a safe and effective delivery system designed to combat non-resectable pancreatic cancer for which currently there is minimal chance of cure.
背景/目的：在过去的 30 年中，胰腺癌病例的预后几乎没有改善，这突出表明迫切需要更有效的治疗方法。显然需要一种能够在肿瘤部位局部输送高浓度化疗药物的药物输送系统。本研究的目的是制造和表征载有吉西他滨的湿纺聚合物纤维的生物物理特性，用于局部药物输送应用。
方法/结果：从海藻酸钠或壳聚糖溶液中纺制的纤维，无论是否含有抗癌药物吉西他滨，都具有均匀的表面积，内部均匀，直径在 50-120μm 之间。药物包封率取决于所使用的聚合物的类型和浓度，范围为 13-52%。吉西他滨显示出一级释放动力学，其中负载药物的 64-82%在最初 10 小时内迅速释放，随后在接下来的 134 小时内持续释放。在用载有吉西他滨的纤维孵育后，观察到离体肿瘤球体生长和细胞活力的时间依赖性抑制，但用对照纤维则没有。
随着进一步的发展，这些研究可能会导致制造出一种安全有效的输送系统，旨在对抗目前治愈机会极小的不可切除的胰腺癌。
