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用于抗菌肽递送的合成黏液生物材料

Synthetic Mucus Biomaterials for Antimicrobial Peptide Delivery.

作者信息

Yang Sydney, Duncan Gregg

机构信息

University of Maryland, Fischell Department of Bioengineering, College Park, MD.

出版信息

bioRxiv. 2023 Mar 9:2023.03.07.531025. doi: 10.1101/2023.03.07.531025.

DOI:10.1101/2023.03.07.531025
PMID:36945438
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10028879/
Abstract

Despite the promise of antimicrobial peptides (AMPs) as treatments for antibiotic-resistant infections, their therapeutic efficacy is limited due to the rapid degradation and low bioavailability of AMPs. To address this, we have developed and characterized a synthetic mucus (SM) biomaterial capable of delivering AMPs and enhancing their therapeutic effect. LL37 loaded SM hydrogels demonstrated controlled release of LL37 over 8 hours as a result of charge-mediated interactions between mucins and LL37 AMPs. Compared to treatment with LL37 alone where antimicrobial activity was reduced after 3 hours, LL37-SM hydrogels inhibited PAO1 growth over 12 hours. LL37-SM hydrogel treatment reduced PAO1 viability over 6 hours whereas a rebound in bacterial growth was observed when treated with LL37 only. These data demonstrate LL37-SM hydrogels enhance antimicrobial activity by preserving LL37 AMP activity and bioavailability. Overall, this work establishes SM biomaterials as a platform for enhanced AMP delivery for antimicrobial applications.

摘要

尽管抗菌肽有望成为治疗抗生素耐药性感染的药物，但其治疗效果因抗菌肽的快速降解和低生物利用度而受到限制。为了解决这个问题，我们开发并表征了一种能够递送抗菌肽并增强其治疗效果的合成黏液（SM）生物材料。由于黏蛋白与LL37抗菌肽之间的电荷介导相互作用，负载LL37的SM水凝胶在8小时内实现了LL37的控释。与单独使用LL37治疗相比，3小时后抗菌活性降低，而LL37-SM水凝胶在12小时内抑制了铜绿假单胞菌PAO1的生长。LL37-SM水凝胶处理在6小时内降低了PAO1的活力，而仅用LL37处理时则观察到细菌生长出现反弹。这些数据表明，LL37-SM水凝胶通过保留LL37抗菌肽的活性和生物利用度来增强抗菌活性。总体而言，这项工作将SM生物材料确立为用于抗菌应用的增强抗菌肽递送的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/10028879/8a43eecbb26b/nihpp-2023.03.07.531025v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/10028879/ff5e53be9d74/nihpp-2023.03.07.531025v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/10028879/63a8c3aa52ce/nihpp-2023.03.07.531025v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/10028879/df3a5a59291a/nihpp-2023.03.07.531025v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/10028879/bf6ae17846ff/nihpp-2023.03.07.531025v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/10028879/8a43eecbb26b/nihpp-2023.03.07.531025v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/10028879/ff5e53be9d74/nihpp-2023.03.07.531025v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/10028879/63a8c3aa52ce/nihpp-2023.03.07.531025v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/10028879/df3a5a59291a/nihpp-2023.03.07.531025v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/10028879/bf6ae17846ff/nihpp-2023.03.07.531025v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/10028879/8a43eecbb26b/nihpp-2023.03.07.531025v1-f0005.jpg

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本文引用的文献

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