A large proportion of
benign prostatic hyperplasia (BPH) patients suffer from
lower urinary tract symptoms after surgery due to the presence of prostatic urothelium
wounds.
Rebamipide (RBM) exerts wound healing promotion and anti-inflammatory effects on various tissues, including the urothelium. However,
intravesical administration of RBM is hindered due to its low solubility and resulting unsustainable drug concentrations in the bladder. In this study, RBM-loaded
chitosan nanoparticles (RBM/CTS NPs) were prepared using the ionic cross-linking method. Physicochemical characteristics and the wound healing promotion effect, as well as in vitro influence on macrophages were evaluated. The results show that RBM/CTS NPs are spherical with uniform size distribution, while slower and sustained in vitro release of RBM is presented. In vivo, faster wound healing and improved re-epithelialization progress were observed
after treatment with RBM/CTS NPs in a model of
thulium laser resection of the prostate (TmLRP). The degree of local inflammatory response decreased, as confirmed by decreasing numbers of pro-inflammatory M1 phenotype macrophages and levels of IL-1β,
IL-6,
IL-12 and TNF-α in the urine of canines. We also found that RBM/CTS NPs suppress macrophage M1 polarization induced by
lipopolysaccharide and
interferon-γ and inhibit the activation of the NF-κB signaling pathway. Therefore, as a novel therapeutic strategy,
intravesical administration of RBM/CTS NPs can effectively avoid drug intolerance and drug wastage, accelerating the postoperative
wound repairing of the prostatic urethra by suppressing macrophage M1 phenotype polarization.