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载地塞米松的核-多壳纳米载体局部应用于对抗口腔黏膜炎症

Topical Application of Dexamethasone-Loaded Core-Multishell Nanocarriers Against Oral Mucosal Inflammation.

作者信息

Yapto Cynthia V, Rajes Keerthana, Inselmann Antonia, Staufenbiel Sven, Stolte Kim N, Witt Maren, Haag Rainer, Dommisch Henrik, Danker Kerstin

机构信息

Institute of Biochemistry, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.

Freie Universität Berlin, Institute of Chemistry and Biochemistry, 14195, Berlin, Germany.

出版信息

Macromol Biosci. 2024 Dec;24(12):e2400286. doi: 10.1002/mabi.202400286. Epub 2024 Oct 3.

Abstract

Topical treatment of oral inflammatory diseases is challenging due to the intrinsic physicochemical barriers of the mucosa and the continuous flow of saliva, which dilute drugs and limit their bioavailability. Nanocarrier technology can be an innovative approach to circumvent these problems and thus improve the efficacy of topical drug delivery to the mucosa. Core-multishell (CMS) nanocarriers are putative delivery systems with high biocompatibility and the ability to adhere to and penetrate the oral mucosa. Ester-based CMS nanocarriers release the anti-inflammatory compound dexamethasone (Dx) more efficiently than a conventional cream. Mussel-inspired functionalization of a CMS nanocarrier with catechol further improves the adhesion of the nanocarrier and may enhance the efficacy of the loaded drugs. In the present study, the properties of the ester-based CMS 10-E-15-350 nanocarrier (CMS-NC) are further evaluated in comparison to the catechol-functionalized variant (CMS-C). While the mucoadhesion of CMS-NC is inhibited by saliva, CMS-C exhibits better mucoadhesion in the presence of saliva. Due to the improved adhesion properties, CMS-C loaded with dexamethasone (Dx-CMS-C) shows a better anti-inflammatory effect than Dx-CMS-NC when applied dynamically. These results highlight the superiority of CMS-C over CMS-NC as an innovative drug delivery system (DDS) for the treatment of oral mucosal diseases.

摘要

由于黏膜固有的物理化学屏障以及唾液的持续流动,会稀释药物并限制其生物利用度,因此口腔炎性疾病的局部治疗具有挑战性。纳米载体技术可能是一种创新方法,可规避这些问题,从而提高局部药物递送至黏膜的疗效。核-多壳(CMS)纳米载体是具有高生物相容性以及能够黏附并穿透口腔黏膜的推定递送系统。基于酯的CMS纳米载体比传统乳膏更有效地释放抗炎化合物地塞米松(Dx)。用儿茶酚对CMS纳米载体进行贻贝启发式功能化可进一步改善纳米载体的黏附性,并可能增强所载药物的疗效。在本研究中,与儿茶酚功能化变体(CMS-C)相比,进一步评估了基于酯的CMS 10-E-15-350纳米载体(CMS-NC)的特性。虽然CMS-NC的黏膜黏附受到唾液抑制,但CMS-C在有唾液存在的情况下表现出更好的黏膜黏附性。由于黏附性能得到改善,动态应用时,载有地塞米松的CMS-C(Dx-CMS-C)比Dx-CMS-NC显示出更好的抗炎效果。这些结果突出了CMS-C作为治疗口腔黏膜疾病的创新药物递送系统(DDS)相对于CMS-NC的优越性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082b/11648588/e618fb346b98/MABI-24-2400286-g001.jpg

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