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支持药物纳米晶体长效递送至粘膜组织的生物粘附低共熔凝胶。

Bioadhesive eutectogels supporting drug nanocrystals for long-acting delivery to mucosal tissues.

作者信息

Bianchi María Beatrice, Zhang Chunyang, Catlin Elise, Sandri Giuseppina, Calderón Marcelo, Larrañeta Eneko, Donnelly Ryan F, Picchio Matías L, Paredes Alejandro J

机构信息

Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100, Pavia, Italy.

School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL, UK.

出版信息

Mater Today Bio. 2022 Oct 25;17:100471. doi: 10.1016/j.mtbio.2022.100471. eCollection 2022 Dec 15.

DOI:10.1016/j.mtbio.2022.100471
PMID:36345362
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9636571/
Abstract

Eutectogels (Egels) are an emerging class of soft ionic materials outperforming traditional temperature-intolerant hydrogels and costly ionogels. Due to their excellent elasticity, non-volatile nature, and adhesion properties, Egels are attracting a great deal of interest in the biomedical space. Herein, we report the first example of adhesive Egels loading drug nanocrystals (Egel-NCs) for controlled delivery to mucosal tissues. These soft materials were prepared using gelatin, glycerine, a deep eutectic solvent (DES) based on choline hydrochloride and glycerol, and nanocrystallised curcumin, a model drug with potent antimicrobial and anti-inflammatory activities. We first explored the impact of the biopolymer concentration on the viscoelastic and mechanical properties of the networks. Thanks to the dynamic interactions between gelatin and the DES, the Egel showed excellent stretchability and elasticity (up to ≈160%), reversible gel-sol phase transition at mild temperature (≈50 ​°C), 3D-printing ability, and good adhesion to mucin protein (stickiness ≈40 ​kPa). release profiles demonstrated the ability of the NCs-based Egel to deliver curcumin for up to four weeks and deposit significantly higher drug amounts in excised porcine mucosa compared to the control cohort. All in all, this study opens new prospects in designing soft adhesive materials for long-acting drug delivery and paves the way to explore novel eutectic systems with multiple therapeutic applications.

摘要

低共熔凝胶(Egels)是一类新兴的软离子材料,性能优于传统的不耐温水凝胶和昂贵的离子凝胶。由于其出色的弹性、不挥发性和粘附性能,Egels在生物医学领域引起了广泛关注。在此,我们报道了首例负载药物纳米晶体的粘附性Egels(Egel-NCs)用于向粘膜组织的控释。这些软材料是使用明胶、甘油、基于胆碱盐酸盐和甘油的低共熔溶剂(DES)以及纳米晶姜黄素制备的,姜黄素是一种具有强大抗菌和抗炎活性的模型药物。我们首先探讨了生物聚合物浓度对网络粘弹性和力学性能的影响。由于明胶和DES之间的动态相互作用,Egel表现出出色的拉伸性和弹性(高达≈160%),在温和温度(≈50℃)下具有可逆的凝胶-溶胶相变、3D打印能力以及对粘蛋白的良好粘附性(粘性≈40kPa)。释放曲线表明,基于纳米晶体的Egel能够在长达四周的时间内递送姜黄素,并且与对照组相比,在切除的猪粘膜中沉积的药物量显著更高。总而言之,本研究为设计用于长效药物递送的软粘附材料开辟了新前景,并为探索具有多种治疗应用的新型低共熔体系铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/10d6a0614b89/gr11.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/0418bc76f529/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/77930771f0ca/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/10d6a0614b89/gr11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/0c8e376f69dd/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/220c24f14986/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/39a54e0ad3aa/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/eeefb9db32f8/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/478c89c2c06a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/b3da0c9571d0/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/2ae7aafb60c0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/294f3316c3a2/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/675adb76eb0e/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/0418bc76f529/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/77930771f0ca/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/9636571/10d6a0614b89/gr11.jpg

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