Reva M Street, Frank H Kung, Laura T Beringer, Daniel B Amchin, Bonnie L Firestein, Caroline L Schauer
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引用次数: 0
摘要
据报道,尿酸(UA)是一种抗氧化剂,对受伤和疾病,特别是中枢神经系统疾病具有神经保护作用。然而,尿酸在水溶液中极难溶解,血清中的高浓度尿酸会导致痛风,这限制了尿酸在人体中的应用。在此,我们开发了一种新型药物递送平台,可持续释放尿酸,应用于神经组织。我们证明,一步法将尿酸掺入电纺明胶/透明质酸纳米纤维垫,可在培养基中控制尿酸的释放。我们采用一种独特的方法,将 12% 的明胶和 1% 的透明质酸在甲酸溶剂中制成溶液,然后加入 UA,制成纳米纤维毡。然后,我们对垫子进行脱氢热交联,并测试其在生理细胞培养基中的尿素释放情况。为了测试纳米纤维毡是否会对健康的神经系统组织产生有害影响,我们在纳米纤维毡上培养脊髓外植体,并评估外植体的延伸情况。我们观察到,无论垫子中 UA 含量多少,脊髓组织延伸出的树突数量和长度都相当。我们的研究结果表明,电纺明胶/透明质酸纳米纤维可用作向神经组织持续输送尿酸的平台,而不会产生有害影响。
Electrospun gelatin/hyaluronic acid nanofibers as a platform for uric acid delivery to neural tissue.
Uric acid (UA) is an antioxidant that has been reported to be a neuroprotective compound for injuries and diseases, and specifically, diseases of the central nervous system. However, uric acid is highly insoluble in aqueous solutions, and high levels in the serum lead to gout, which limits its use in humans. Here, we develop a novel drug delivery platform that will release uric acid in a sustained manner for application to neural tissue. We demonstrate that one-step incorporation of UA into an electrospun gelatin/hyaluronic acid nanofiber mat results in controlled release of UA in culture medium. Taking a unique approach, we made solutions of 12% gelatin and 1% hyaluronic acid in a formic acid solvent and added UA for production of nanofiber mats. We then dehydrothermally crosslinked the mats and tested for release of UA into physiological cell culture medium. To test whether the mats have any detrimental effects on healthy nervous system tissue, we cultured spinal cord explants on the mats extended and assessed extensions from the explants. We observed that comparable numbers and lengths of dendrites are extended from the spinal cord tissue, regardless of the amount UA content in the mats. Our results suggest that electrospun gelatin/hyaluronic acid nanofibers can be used as a platform for sustained uric acid delivery to neural tissue without detrimental effects.
期刊介绍:
Biotechnology Progress , an official, bimonthly publication of the American Institute of Chemical Engineers and its technological community, the Society for Biological Engineering, features peer-reviewed research articles, reviews, and descriptions of emerging techniques for the development and design of new processes, products, and devices for the biotechnology, biopharmaceutical and bioprocess industries.
Widespread interest includes application of biological and engineering principles in fields such as applied cellular physiology and metabolic engineering, biocatalysis and bioreactor design, bioseparations and downstream processing, cell culture and tissue engineering, biosensors and process control, bioinformatics and systems biology, biomaterials and artificial organs, stem cell biology and genetics, and plant biology and food science. Manuscripts concerning the design of related processes, products, or devices are also encouraged. Four types of manuscripts are printed in the Journal: Research Papers, Topical or Review Papers, Letters to the Editor, and R & D Notes.