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含苯妥英钠和维生素C的电纺羧甲基壳聚糖/聚环氧乙烷纳米纤维的药物释放、细胞黏附及伤口愈合评估

Drug release, cell adhesion and wound healing evaluations of electrospun carboxymethyl chitosan/polyethylene oxide nanofibres containing phenytoin sodium and vitamin C.

作者信息

Zarandi Mohammad Amin, Zahedi Payam, Rezaeian Iraj, Salehpour Alireza, Gholami Mehdi, Motealleh Behrooz

机构信息

School of Chemical Engineering, College of Engineering, University of Tehran, P. O. Box: 11155-4563, Tehran, Iran.

Faculty of Pharmacy, and Pharmaceutical Sciences Research Center and Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran.

出版信息

IET Nanobiotechnol. 2015 Aug;9(4):191-200. doi: 10.1049/iet-nbt.2014.0030.

Abstract

In this work, N, O-carboxymethyl chitosan (CMCS) samples from virgin chitosan (CS) were synthesised and CMCS/polyethylene oxide (PEO) (50/50) blend nanofibrous samples were successfully electrospun from their aqueous solution. The electrospinning conditions to achieve smooth and fine diameter nanofibrous mats were optimised via D-optimal design approach. Afterwards, vitamin C and phenytoin sodium (PHT-Na) were added to these samples for producing wound dressing materials. H-nuclear magnetic resonance, scanning electron microscopy and Fourier transform infrared tests for the evaluation of functionalised CS, morphology and biodegradability studies of CMCS/PEO blend nanofibrous samples were applied. The kinetic and drug release mechanism for vitamin C and PHT-Na drug-loaded electrospun samples were also investigated by UV-vis spectrophotometer and high performance liquid chromatography, respectively. The results showed an approximately similar drug release rate of the two drugs and followed Higuchi's kinetic model. The stem cells viability and their adhesion on the surface of the samples containing PHT-Na and vitamin C were carried out using MTT assay and the best cells' biocompatibility was obtained using both drugs into the CMCS/PEO nanofibrous samples. Moreover, the in vivo animal wound model results revealed that the electrospun samples containing vitamin C and PHT-Na (1%) had a remarkable efficiency in the wounds' closure and their healing process compared with vitamin C/PHT-Na (50/50) ointment. Finally, the histology observations showed that the wound treated with optimised electrospun samples containing two drugs enabled regeneration of epidermis layers due to collagen fibres accumulation followed by granulating tissues formation without necrosis.

摘要

在本研究中,由天然壳聚糖(CS)合成了N,O-羧甲基壳聚糖(CMCS)样品,并成功地从其水溶液中静电纺丝制备了CMCS/聚环氧乙烷(PEO)(50/50)共混纳米纤维样品。通过D-最优设计方法优化了制备光滑且直径细小的纳米纤维毡的静电纺丝条件。之后,向这些样品中添加维生素C和苯妥英钠(PHT-Na)以制备伤口敷料材料。应用氢核磁共振、扫描电子显微镜和傅里叶变换红外测试来评估功能化壳聚糖、CMCS/PEO共混纳米纤维样品的形态和生物降解性。还分别通过紫外可见分光光度计和高效液相色谱研究了负载维生素C和PHT-Na的静电纺丝样品的动力学和药物释放机制。结果表明两种药物的释放速率大致相似,且符合Higuchi动力学模型。使用MTT法检测了含有PHT-Na和维生素C的样品表面干细胞的活力及其黏附情况,将两种药物添加到CMCS/PEO纳米纤维样品中时获得了最佳的细胞生物相容性。此外,体内动物伤口模型结果显示,与维生素C/PHT-Na(50/50)软膏相比,含有维生素C和PHT-Na(1%)的静电纺丝样品在伤口闭合及其愈合过程中具有显著效果。最后,组织学观察表明,用含有两种药物的优化静电纺丝样品处理的伤口,由于胶原纤维的积累,随后形成肉芽组织且无坏死,从而实现了表皮层的再生。

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