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Rebamipide-loaded chitosan nanoparticles accelerate prostatic wound healing by inhibiting M1 macrophage-mediated inflammation via the NF-κB signaling pathway
- Source :
- Biomaterials Science. 8:912-925
- Publication Year :
- 2020
- Publisher :
- Royal Society of Chemistry (RSC), 2020.
-
Abstract
- 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.
- Subjects :
- Male
Lipopolysaccharide
Drug Compounding
Prostatic Hyperplasia
Biomedical Engineering
Inflammation
02 engineering and technology
Quinolones
03 medical and health sciences
chemistry.chemical_compound
Dogs
In vivo
Prostate
medicine
Animals
Humans
Macrophage
General Materials Science
Urothelium
Cell Proliferation
030304 developmental biology
Chitosan
Wound Healing
0303 health sciences
Alanine
Macrophages
NF-kappa B
021001 nanoscience & nanotechnology
medicine.anatomical_structure
chemistry
Cancer research
Nanoparticles
Rebamipide
medicine.symptom
0210 nano-technology
Wound healing
medicine.drug
Subjects
Details
- ISSN :
- 20474849 and 20474830
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Biomaterials Science
- Accession number :
- edsair.doi.dedup.....fde35fa5e5b5fd8d06e7d932629e431f