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

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-17A) 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.

Molecular mechanism and promising treatments of chronic prostatitis/chronic pelvic pain syndrome: An exploratory bibliometric analysis and literature review of preclinical studies

“…This might be a promising therapy in the future. And Yang et al developed pH/ROS dual‐responsive dexamethasone (Dex) nanoformulations which might regulate oxidative stress, and found it was effective for the management of CP/CPPS mice and alleviation of depression in mice [ 75 ] . Although these mechanisms were widely used in preclinical studies to explore some interventions for the treatment of CP/CPPS, such as electroacupuncture might regulate TLR4/NF‐κB signaling pathway to relieve pelvic pain and attenuate prostatic inflammation in estradiol‐induced CNP rats [ 60 ] , Poria cocos polysaccharides could alleviate CNP by regulating the gut microbiota [ 70 ] , and low‐intensity extracorporeal shock wave therapy might reduce inflammation and pain in EAP rats via PI3K/AKT/FOXO1 pathway [ 51 ] , translational studies based on these mechanisms were actually quite rare.…”