Spinal cord injury (SCI) is a devastating disease that can cause persistent damage to urinary system. Rapid and significant changes in the barrier function and aggravated inflammation have been found in bladder at the earliest stage of acute SCI. Early intervention for the pathological changes of bladder caused by SCI may protect the bladder function and prevent the long-term urinary complications. In the present study, we designed and constructed a polydopamine nanosystem containing pirfenidone, aiming to alleviate bladder inflammation and preserve bladder function through intravesical instillation at early stage of acute SCI.

A polydopamine-based drug delivery system carrying pirfenidone (PFD@PDA NPs) was designed. The capability of penetration and retention of PFD@PDA NPs in bladder was evaluated. The effects of intravesical stellation of PFD@PDA NPs on the bladder inflammation and oxidative stress caused by SCI was assessed. The urodynamic parameters of SCI animal were determined and the effect of PFD@PDA NPs on the urodynamic parameters of SCI animal was also evaluated.

PFD@PDA NPs system could effectively penetrate the bladder wall and stay in bladder tissue for at least two days. It significantly alleviated bladder inflammation and urothelial hyperplasia caused by acute complete SCI. PFD@PDA NPs inhibited the expression of inflammatory mediators and the proportion of proinflammatory macrophages, mitigating the elevated oxidative stress levels. In addition, PFD@PDA NPs significantly improved the unfavorable urodynamic parameters at the early stage of SCI.

In clinic, patients with spinal cord injury are usually accompanied by complicated urinary complications, such as urinary retention, chronic bladder inflammation and recurrent urinary tract infection. The most serious consequence of spinal cord injury is that these complications may eventually develop into hydronephrosis and renal failure, which greatly increases patient mortality. Currently, the treatment methods for bladder dysfunction caused by spinal cord injury are very limited, usually symptomatic treatment for bladder overactivity, but there are currently no specific drugs to treat bladder dysfunction. We designed and constructed a PFD@PDA NPs system, which could effectively alleviate bladder inflammation and protect bladder function at the early stage of SCI. Early intravesical application of PFD@PDA NPs to SCI patients may help preserve bladder function, reduce the susceptibility to UTIs and improve the patients’ quality of life. The present study also provides valuable insight into the development of intravesical drug delivery platforms for bladder dysfunction.

These results demonstrated the feasibility of PFD@PDA NPs as a robust treatment to suppress inflammation and preserve bladder-filling function at the early stage of acute SCI. Early intravesical use of PFD@PDA NPs should be recommended for patients with SCI after clinical trials.