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糖皮质激素纳米制剂可缓解慢性盆腔疼痛综合征,并可能缓解小鼠的抑郁症状。

Glucocorticoid nanoformulations relieve chronic pelvic pain syndrome and may alleviate depression in mice.

机构信息

Department of Urology, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, 400038, China.

Department of Chemistry, College of Basic Medicine, Army Medical University, Third Military Medical University, Chongqing, 400038, China.

出版信息

J Nanobiotechnology. 2023 Jun 21;21(1):198. doi: 10.1186/s12951-023-01893-4.

Abstract

BACKGROUND

Chronic pelvic pain syndrome (CPPS) is a typical symptom of chronic prostatitis (CP) in males that may cause abnormal urination, sexual dysfunction, or depression and significantly affect the quality of life of the patient. Currently, there is no effective treatment for CPPS due to its recurrence and intractability. For synergistic CPPS therapy, we developed pH/reactive oxygen species (ROS) dual-responsive dexamethasone (Dex) nanoformulations using a ROS-responsive moiety and phytochemical modified α-cyclodextrin (α-CD) as the carrier.

RESULTS

Dex release from the nanoformulations can be controlled in acidic and/or ROS-rich microenvironments. The fabricated Dex nanoformulations can also be efficiently internalized by lipopolysaccharide (LPS)-stimulated macrophages, prostatic epithelial cells, and stromal cells. Moreover, the levels of proinflammatory factors (e.g., TNF-α, IL-1β, and IL-17 A) in these cells were significantly decreased by Dex nanoformulations treatment through the release of Dex, phytochemical and elimination of ROS. In vivo experiments demonstrated notable accumulation of the Dex nanoformulations in prostate tissue to alleviate the symptoms of CPPS through the downregulation of proinflammatory factors. Interestingly, depression in mice may be relieved due to alleviation of their pelvic pain.

CONCLUSION

We fabricated Dex nanoformulations for the effective management of CPPS and alleviation of depression in mice.

摘要

背景

慢性骨盆疼痛综合征(CPPS)是男性慢性前列腺炎(CP)的一种典型症状,可能导致排尿异常、性功能障碍或抑郁,并显著影响患者的生活质量。目前,由于 CPPS 的复发和难治性,尚无有效的治疗方法。为了协同治疗 CPPS,我们使用 ROS 响应部分和植物化学修饰的α-环糊精(α-CD)作为载体,开发了 pH/活性氧(ROS)双重响应地塞米松(Dex)纳米制剂。

结果

纳米制剂中 Dex 的释放可以在酸性和/或富含 ROS 的微环境中得到控制。所制备的 Dex 纳米制剂还可以被脂多糖(LPS)刺激的巨噬细胞、前列腺上皮细胞和基质细胞有效内化。此外,Dex 纳米制剂通过 Dex 的释放、植物化学物质的消除和 ROS 的消除,显著降低了这些细胞中促炎因子(如 TNF-α、IL-1β 和 IL-17A)的水平。体内实验表明,Dex 纳米制剂在前列腺组织中的显著积累,通过下调促炎因子,缓解 CPPS 的症状。有趣的是,由于缓解了它们的骨盆疼痛,小鼠的抑郁可能会得到缓解。

结论

我们制备了 Dex 纳米制剂,用于有效管理 CPPS 和缓解小鼠的抑郁。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6809/10283268/9b44f38535e5/12951_2023_1893_Fig1_HTML.jpg

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