Abstract

This study aims to develop a novel device with nanofiber membrane capable of sustained release of temozolomide (TMZ) and neuron growth factor (NGF). An improved bio-availability of TMZ and NGF in surroundings proximal to the device was expected to be attained for a prolonged period of time. The device was developed by integrating TMZ-doped polycaprolactone (PCL) nanofiber (TP) membrane and NGF-coated PCL (NGFP) membrane using sodium alginate hydrogel. TP was prepared by direct electrospinning of TMZ/PCL. NGFP membrane was developed by layer-by-layer assembling technology. The incorporation of TMZ-doped nanofiber and NGFP nanofiber in the device was confirmed by scanning electron microscopy. The number of NGF layer in NGF-coated PCL membrane could be readily measured with energy spectrum analysis. The in vitro release study showed that TP-NGFP-TP membrane could efficiently liberate TMZ to inhibit the growth of C6 glioma cells, and sufficient NGF to induce the differentiation of PC12 neuron cells over four weeks. Such TP-NGFP-TP membrane device can be employed as a tampon to fill up surgical residual cavity and afford residual glioma removal, structural support, hemostasis, and local neural tissue reconstruction in the surgical treatment of glioma. The study opens a horizon to develop multifunctional biomaterial device for maximized glioma treatment efficacy.

Highlights

  • Gliomas have been the most severe brain tumors [1]

  • It was found that this device still retained the ability to induce the differentiation of PC12 cells (Fig D in S1 File). These results suggested that sufficient neuron growth factor (NGF) layer, i.e. adequate NGF content, in NGF-coated PCL (NGFP) membrane is critical to induce neural cell differentiation and in turn potential neural tissue reconstruction

  • Such device plays a dual role in inhibiting in vitro growth of glioma cells and improving the differentiation of neuron cells. Such a membrane device could have high potential to be used as surgical residual cavity tampon to improve the local bioavailability of TMZ and NGF, exerting strengthened on site effects on prevention of glioma recurrence and metastasis, reduction of chemo side effect and acceleration of the local neural tissue reconstruction in the treatment of glioma

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Summary

Introduction

Gliomas have been the most severe brain tumors [1]. The incidence of gliomas is relative to 80% of malignant brain tumors [2]. Surgical resection is the key procedure of glioma treatment. Surgical residual cavity and its proximal surroundings are usually the breeding sites of recurrence or metastasis arisen from residual tumor cells due to robust invasiveness property of PLOS ONE | DOI:10.1371/journal.pone.0161435. Nanofiber Membrane to Prevent Glioma Recurrence and Improve Local Neural Tissue Reconstruction Surgical residual cavity and its proximal surroundings are usually the breeding sites of recurrence or metastasis arisen from residual tumor cells due to robust invasiveness property of PLOS ONE | DOI:10.1371/journal.pone.0161435 August 22, 2016

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