Codelivery of 1α,25-Dihydroxyvitamin D(3) and CYP24A1 Inhibitor VID400 by Nanofiber Dressings Promotes Endogenous Antimicrobial Peptide LL-37 Induction.
Codelivery of 1α,25-Dihydroxyvitamin D(3) and CYP24A1 Inhibitor VID400 by Nanofiber Dressings Promotes Endogenous Antimicrobial Peptide LL-37 Induction.
复制标题
纳米纤维敷料共递送1α,25 - 二羟基维生素D₃与CYP24A1抑制剂VID400可促进内源性抗菌肽LL - 37的诱导生成。
DOI：
10.1021/acs.molpharmaceut.1c00944
复制
发表时间：
2022-03-07
影响因子：
4.9
通讯作者：
Xie, Jingwei
中科院分区：
文献类型：
--
作者：
Su, Yajuan;Ganguli-Indra, Gitali;Bhattacharya, Nilika;Logan, Isabelle E.;Indra, Arup K.;Gombart, Adrian F.;Wong, Shannon L.;Xie, Jingwei
关键词：
手术部位感染是一个重要的临床问题。在此，本研究旨在开发一种基于纳米纤维的敷料，能够局部持续递送免疫调节化合物，包括1α，25-二羟基维生素D3（1，25（OH）2D 3）和VID 400（一种CYP 24 A1抑制剂），用于诱导内源性凯萨林菌素抗菌肽（CAMP）基因的表达，该基因编码hCAP 18蛋白，该蛋白被加工成LL-37肽。采用静电纺丝法制备了1，25（OH）2D 3和VID 400共包封的纳米纤维伤口敷料。1，25（OH）2D 3和VID 400均成功地装载到纳米纤维中，包封率大于90%，并在4周内从纳米纤维中持续释放。用1，25（OH）2D 3/VID 400共负载的聚（β-己内酯）纳米纤维处理显著诱导体外单核细胞、中性粒细胞和角质形成细胞中的hCAP 18/LL-37表达。此外，1，25（OH）2D 3/VID 400膜的给药显著增加了人CAMP转基因小鼠皮肤伤口和人皮肤外植体人工伤口中hCAP 18/LL-37的表达。含1，25（OH）2D 3和VID 400的生物敷料通过诱导抗菌肽产生，比单独的游离药物或负载1，25（OH）2D 3的纳米纤维更有效地增强先天免疫。总之，本研究中提供的1，25（OH）2D 3/VID 400包埋敷料显示出预防手术部位感染的潜力。
Surgical site infections represent a significant clinical problem. Herein, this study aimed to develop a nanofiber-based dressing capable of local sustained delivery of immunomodulating compounds including 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and VID400, a CYP24A1 inhibitor, for inducing expression of the endogenous cathelicidin antimicrobial peptide (CAMP) gene which encodes the hCAP18 protein that is processed into the LL-37 peptide. Nanofiber wound dressings with co-encapsulation of 1,25(OH)2D3 and VID400 were prepared by electrospinning. Both 1,25(OH)2D3 and VID400 were successfully loaded into nanofibers with encapsulation efficiencies larger than 90% and exhibited a sustained release from nanofibers over 4 weeks. Treatment with 1,25(OH)2D3/VID400-co-loaded poly(ϵ-caprolactone) nanofibers significantly induced hCAP18/LL-37 expression in monocytes, neutrophils, and keratinocytes in vitro. In addition, administration of 1,25(OH)2D3/VID400 nanofiber membranes dramatically increased expression of hCAP18/LL-37 in skin wounds of human CAMP transgenic mice and artificial wounds of human skin explants. The 1,25(OH)2D3 and VID400 containing nanofiber dressings enhanced innate immunity by inducing antimicrobial peptide production more efficiently than free drug alone or 1,25(OH)2D3 loaded nanofibers. Together, 1,25(OH)2D3/VID400 embedded nanofiber dressings presented in this study show potential in preventing surgical site infections.
登录
查看更多内容
影响因子：
15.9
作者：
Bai, Xiuying;Miao, Dengshun;Karaplis, Andrew C.
通讯作者：
Karaplis, Andrew C.
影响因子：
56.9
作者：
Liu, PT;Stenger, S;Modlin, RL
通讯作者：
Modlin, RL
DOI：
10.1016/j.ecl.2010.02.010
发表时间：
2010-06
影响因子：
4.5
作者：
Hewison, Martin
通讯作者：
Hewison, Martin
DOI：
10.1016/j.jsbmb.2019.105552
发表时间：
2020-04-01
影响因子：
4.1
作者：
Lowry, Malcolm B.;Guo, Chunxiao;Gombart, Adrian F.
通讯作者：
Gombart, Adrian F.
影响因子：
2
作者：
Eagye, Kathryn J.;Kim, Aryun;Nicolau, David P.
通讯作者：
Nicolau, David P.