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Int J Nanomedicine ; 19: 8353-8371, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39161357

RESUMEN

Introduction: Overactive bladder (OAB) is a highly prevalent condition with limited treatment options due to poor efficacy, side effects, and patient compliance. Novel drug delivery systems that can target the bladder wall may improve OAB therapy. Methods: We explored a polydopamine (PDA)-coated lactobacillus platform as a potential carrier for localized OAB treatment. Urinary microbiome profiling was performed to identify the presence of lactobacillus in healthy and OAB groups. Lactobacillus-PDA nanoparticles were synthesized and characterized by electron microscopy and spectrophotometry. A rat bladder perfusion model and human bladder smooth muscle cell spheroids were used to assess the distribution and penetration of the nanoparticles. The efficacy of the Lactobacillus-PDA system (LPS) for delivering the antimuscarinic drug solifenacin was evaluated in an OAB rat model. Results: Urinary microbiome profiling revealed lactobacillus as a dominant genus in both healthy and OAB groups. The synthesized Lactobacillus-PDA nanoparticles exhibited uniform size and optical properties. In the rat bladder perfusion model, the nanoparticles distributed throughout the bladder wall and smooth muscle without toxicity. The nanoparticles also penetrated human bladder smooth muscle cell spheroids. In the OAB rat model, LPS facilitated the delivery of solifenacin and improved treatment efficacy. Discussion: The results highlight LPS as a promising drug carrier for targeted OAB therapy via penetration into bladder tissues. This bacteriotherapy approach may overcome limitations of current systemic OAB medications. Lactobacillus, a probiotic bacterium present in the urinary tract microbiome, was hypothesized to adhere to and penetrate the bladder wall when coated with PDA nanoparticles, making it a suitable candidate for localized drug delivery.


Asunto(s)
Indoles , Lactobacillus , Microbiota , Polímeros , Vejiga Urinaria Hiperactiva , Vejiga Urinaria , Animales , Indoles/química , Indoles/farmacocinética , Vejiga Urinaria Hiperactiva/terapia , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Humanos , Polímeros/química , Microbiota/efectos de los fármacos , Ratas , Esferoides Celulares , Succinato de Solifenacina/farmacocinética , Succinato de Solifenacina/química , Succinato de Solifenacina/administración & dosificación , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Femenino , Miocitos del Músculo Liso/efectos de los fármacos , Antagonistas Muscarínicos/farmacocinética , Antagonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/química , Antagonistas Muscarínicos/administración & dosificación , Portadores de Fármacos/química
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