The sustained release of a water-soluble drug is always a key and important issue in pharmaceutics. In this study, using cellulose acetate (CA) as a biomacromolecular matrix, core-sheath nanofibers were developed for providing a sustained release of a model drug—metformin hydrochloride (MET). The core–sheath nanofibers were fabricated using modified tri-axial electrospinning, in which a detachable homemade spinneret was explored. A process—nanostructure–performance relationship was demonstrated through a series of characterizations. The prepared nanofibers F2 could release 95% of the loaded MET through a time period of 23.4 h and had no initial burst effect. The successful sustained release performances of MET can be attributed to the following factors: (1) the reasonable application of insoluble CA as the filament-forming carrier, which determined that the drug was released through a diffusion manner; (2) the core–sheath nanostructure provided the possibility of both encapsulating the drug completely and realizing the heterogeneous distributions of MET in the nanofibers with a higher drug load core than the sheath; (3) the thickness of the sheath sections were able to be exploited for further manipulating a better drug extended release performance. The mechanisms for manipulating the drug sustained release behaviors are proposed. The present proof-of-concept protocols can pave a new way to develop many novel biomolecule-based nanostructures for extending the release of water-soluble drugs.

中文翻译：

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核-鞘纳米结构内药物的异质分布对其缓释特性的影响


水溶性药物的缓释一直是药剂学中的关键和重要问题。在这项研究中，使用醋酸纤维素（CA）作为生物大分子基质，开发了核鞘纳米纤维，用于提供模型药物盐酸二甲双胍（MET）的持续释放。采用改进的三轴静电纺丝技术制备了芯鞘纳米纤维，其中探索了可拆卸的自制喷丝头。通过一系列表征证明了工艺-纳米结构-性能关系。制备的纳米纤维F2可以在23.4小时内释放95%的负载MET，并且没有初始爆发效应。 MET成功的缓释性能可归因于以下因素：（1）不溶性CA作为成丝载体的合理应用，决定了药物通过扩散方式释放； (2)核-鞘纳米结构提供了既完全包裹药物又实现MET在纳米纤维中的非均质分布的可能性，且核载量高于鞘； (3)能够利用鞘部分的厚度来进一步操纵更好的药物缓释性能。提出了操纵药物缓释行为的机制。目前的概念验证方案可以为开发许多新颖的基于生物分子的纳米结构以延长水溶性药物的释放铺平道路。