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基于 TGF-α 和 TGF-β1 的泊洛沙姆胶束/水凝胶复合材料:一种有前途的治疗嗅觉障碍的新型候选药物。

A TGF-α and TGF-β1 Poloxamer-based micelle/hydrogel composite: A promising novel candidate for the treatment of anosmia.

机构信息

Department of Life Science Engineering, Faculty of New Science and Technology, University of Tehran, Tehran, Iran.

ENT and Head and Neck Research Center and Department, The Five Senses Health Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Biotechnol Prog. 2022 Nov;38(6):e3294. doi: 10.1002/btpr.3294. Epub 2022 Aug 31.

Abstract

Anosmia is the inability to smell or loss of the sense of smell. It can reduce your ability to detect the smell of smoke, gas leaks, or spoiled food, as well as hinder the quality of life related to social interactions and feelings of well-being. In the current study, a drug delivery composite was designed to cure anosmia and its efficiency in delivering transforming growth factor alpha (TGF-α) and transforming growth factor beta 1 (TGF-β1) to the nasal cavity was evaluated. Bovine serum albumin (BSA) was used as a model protein for encapsulation into Poloxamers 407 micelles. For the optimization of the BSA-micelle formulation, a two-parameter five-level central composite design (CCD) was applied. The BSA-micelle was optimized with a particle size of 41 nm, drug loading of 8%, and encapsulation efficiency of 74%. Further, the BSA-micelle was characterized by FESEM, TEM, and FTIR. The analysis of release profile suggested high-paced free BSA release compared to the gradual and prolonged release of BSA-micelle/hydrogel and BSA-micelles. The cytotoxicity assay demonstrated the safety of TGF-α and TGF-β1-micelles/hydrogel. Moreover, it was observed that TGF-α and TGF-β1 within the hydrogels promote cellular viability and human olfactory ectomesenchymal stem cell OE-MSCs proliferation. In conclusion, According to the results of our study, the TGF-α and TGF-β1-micelle/hydrogel-based delivery system provides a suitable alternative for anosmia treatment.

摘要

嗅觉丧失是指无法闻到或失去嗅觉的能力。它会降低你检测烟雾、气体泄漏或变质食物的能力,也会影响到与社交互动和幸福感相关的生活质量。在目前的研究中,设计了一种药物输送复合材料来治疗嗅觉丧失,并评估其将转化生长因子 alpha (TGF-α) 和转化生长因子 beta 1 (TGF-β1) 输送到鼻腔的效率。牛血清白蛋白 (BSA) 被用作包封到泊洛沙姆 407 胶束中的模型蛋白。为了优化 BSA-胶束配方,应用了两参数五水平中心组合设计 (CCD)。BSA-胶束的优化粒径为 41nm,载药量为 8%,包封效率为 74%。此外,还通过 FESEM、TEM 和 FTIR 对 BSA-胶束进行了表征。释放曲线分析表明,与 BSA-胶束/水凝胶和 BSA-胶束的缓慢和持续释放相比,游离 BSA 的释放速度更快。细胞毒性试验表明 TGF-α 和 TGF-β1-胶束/水凝胶的安全性。此外,还观察到水凝胶中的 TGF-α 和 TGF-β1 促进了细胞活力和人嗅外胚层间充质干细胞 OE-MSCs 的增殖。总之,根据我们的研究结果,TGF-α 和 TGF-β1-胶束/水凝胶递送系统为治疗嗅觉丧失提供了一种合适的替代方案。

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