1. Academic Validation
  2. Lactobacillus-Polydopamine System for Targeted Drug Delivery in Overactive Bladder: Evidence from Bladder Cell Spheroids, Rat Models, and Urinary Microbiome Profiling

Lactobacillus-Polydopamine System for Targeted Drug Delivery in Overactive Bladder: Evidence from Bladder Cell Spheroids, Rat Models, and Urinary Microbiome Profiling

  • Int J Nanomedicine. 2024 Aug 15:19:8353-8371. doi: 10.2147/IJN.S465745.
Xiaolong Wang # 1 2 Guanyi Wang # 2 Peibin Cen # 1 Hongyu Lan 1 Linfa Guo 2 Zuhaer Yisha 2 Aodun Gu 2 Guiyong Liu 3 Zijian Wang 2 Tongzu Liu 2 4 5 6 7 8 Qingfeng Yu 1 9 10 11
Affiliations

Affiliations

  • 1 Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
  • 2 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China.
  • 3 Department of Urology, Qianjiang Central Hospital of Hubei Province, Qianjiang, People's Republic of China.
  • 4 Hubei Key Laboratory of Urological Diseases, Wuhan University, Wuhan, People's Republic of China.
  • 5 Hubei Clinical Research Center for Laparoscopic/Endoscopic Urologic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China.
  • 6 Institute of Urology, Wuhan University, Wuhan, People's Republic of China.
  • 7 Hubei Medical Quality Control Center for Laparoscopic/Endoscopic Urologic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China.
  • 8 Wuhan Clinical Research Center for Urogenital Tumors, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China.
  • 9 Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou Medical University, Guangzhou, People's Republic of China.
  • 10 Guangdong Engineering Research Center of Urinary Minimally Invasive Surgery Robot and Intelligent Equipment, Guangzhou Medical University, Guangzhou, People's Republic of China.
  • 11 Guangzhou Institute of Urology, Guangzhou Medical University, Guangzhou, People's Republic of China.
  • # Contributed equally.
Abstract

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.

Keywords

drug delivery; lactobacillus; nano material; overactive bladder; polydopamine.

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