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新型β-葡聚糖水凝胶喷雾制剂的研制及其在 db/db 糖尿病小鼠模型中的伤口愈合功效。

Development of a novel beta-glucan supplemented hydrogel spray formulation and wound healing efficacy in a db/db diabetic mouse model.

机构信息

Biotec BetaGlucans AS, Tromsø 9019, Norway; Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø 9037, Norway.

Biotec BetaGlucans AS, Tromsø 9019, Norway.

出版信息

Eur J Pharm Biopharm. 2021 Dec;169:280-291. doi: 10.1016/j.ejpb.2021.10.013. Epub 2021 Oct 30.

DOI:10.1016/j.ejpb.2021.10.013
PMID:34728362
Abstract

To relieve the severe economic and social burdens and patient suffering caused by the increasing incidence of chronic wounds, more effective treatments are urgently needed. In this study, we focused on developing a novel sprayable wound dressing with the active ingredient β-1,3/1,6-glucan (βG). Since βG is already available as the active ingredient in a commercial wound healing product provided as a hydrogel in a tube (βG-Gel), the sprayable format should bring clinical benefit by being easily sprayed onto wounds; whilst retaining βG-Gel's physical stability, biological safety and wound healing efficacy. Potentially sprayable βG hydrogels were therefore formulated, based on an experimental design setup. One spray formulation, named βG-Spray, was selected for further investigation, as it showed favorable rheological and spraying properties. The βG-Spray was furthermore found to be stable at room temperature for more than a year, retaining its rheological properties and sprayability. The cytotoxicity of βG-Spray in keratinocytes in vitro, was shown to be promising even at the highest tested concentration of 100 μg/ml. The βG-Spray also displayed favorable fluid affinity characteristics, with a capacity to both donate and absorb close to 10% fluid relative to its own weight. Finally, the βG-Spray was proven comparably effective to the commercial product, βG-Gel, and superior to both the water and the carrier controls (NoβG-Spray), in terms of its ability to promote wound healing in healing-impaired animals. Contraction was found to be the main wound closure mechanism responsible for the improvement seen in the βG-treatment groups (βG-Spray and βG-Gel). In conclusion, the novel sprayable βG formulation, confirmed its potential to expand the clinical use of βG as wound dressing.

摘要

为了缓解不断增加的慢性伤口给患者带来的严重经济和社会负担及痛苦,我们迫切需要更有效的治疗方法。在本研究中,我们专注于开发一种新型的可喷涂伤口敷料,其有效成分为β-1,3/1,6-葡聚糖(βG)。由于βG 已经作为一种商用伤口愈合产品的有效成分存在,该产品为管装水凝胶形式(βG-Gel),因此可喷涂形式应该通过容易喷涂到伤口上为临床带来益处;同时保持βG-Gel 的物理稳定性、生物安全性和伤口愈合功效。因此,我们基于实验设计方案,配制了潜在的可喷涂βG 水凝胶。一种名为βG-Spray 的喷涂配方被选中进行进一步研究,因为它显示出良好的流变学和喷涂性能。此外,βG-Spray 在室温下稳定超过一年,保持其流变学特性和可喷涂性。βG-Spray 在体外角质形成细胞中的细胞毒性研究表明,即使在最高测试浓度 100μg/ml 下,也具有很大的应用潜力。βG-Spray 还表现出良好的流体亲和特性,其容量能够相对于其自身重量捐献和吸收接近 10%的液体。最后,βG-Spray 在促进愈合受损动物伤口愈合的能力方面,被证明与商用产品βG-Gel 相当,并且优于水和载体对照(NoβG-Spray)。研究发现收缩是导致βG 治疗组(βG-Spray 和βG-Gel)伤口改善的主要伤口闭合机制。总之,新型可喷涂βG 配方证实了其作为伤口敷料扩大βG 临床应用的潜力。

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