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应用两阶段实验设计与优化方法制备用于靶向治疗尿路感染的高包封率环丙沙星负载牛血清白蛋白纳米粒

Application of a Two-Phase Experiment Design and Optimization Method to Formulate Ciprofloxacin-Loaded Bovine Serum Albumin Nanoparticles with High-Entrapment Efficiency for Targeting Urinary Tract Infections.

作者信息

Sánchez Sofía V, Cruz Jorge Erlen, Navarro M Nicolás, González María José, Vásquez Ricardo, Del Canto Felipe, Scavone Paola, Arrúa Eva C, Morales Javier O

机构信息

Facultad de Ciencias Químicas y Farmacéuticas, Departamento de Ciencia Y Tecnología Farmacéutica, Universidad de Chile, Laboratorio Drug Delivery, Santiago, Chile.

Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile.

出版信息

AAPS PharmSciTech. 2025 May 2;26(5):122. doi: 10.1208/s12249-025-03115-6.

Abstract

Urinary tract infections (UTIs), predominantly caused by uropathogenic Escherichia coli (UPEC), pose a global health concern due to rising antibiotic resistance and biofilm formation. Albumin nanoparticles (NPs) offer a promising strategy for UTI treatment, with site-specific selectivity, improved bioavailability, and sustained drug release. This study focused on developing an optimized method for formulating ciprofloxacin-loaded albumin nanoparticles (CPF-loaded BSA NPs) to treat UPEC and its biofilms effectively. A desolvation method was used to synthesize the nanoparticles, and a two-phase experimental design was used for optimization. Evaluation parameters included size, polydispersity index, zeta potential, morphology, encapsulation efficiency, drug release, storage stability, cytotoxicity, and effectiveness against UPEC. The optimized CPF-loaded BSA NPs exhibited desirable characteristics such as small particle size (123 nm), low polydispersity index (0.178), optimum zeta potential (-31.8), and high encapsulation efficiency (> 80%). They also exhibited low cytotoxicity, high stability, and sustained drug release, making them an ideal drug delivery system. Critically, they demonstrated effectiveness against UPEC and its biofilm. This study suggests that the optimized CPF-loaded BSA NPs, synthesized using our optimized desolvation technique, hold the potential for effectively treating UTIs caused by UPEC.

摘要

尿路感染(UTIs)主要由尿路致病性大肠杆菌(UPEC)引起,由于抗生素耐药性增加和生物膜形成,已成为全球关注的健康问题。白蛋白纳米颗粒(NPs)为UTI治疗提供了一种有前景的策略,具有位点特异性选择性、提高的生物利用度和持续的药物释放。本研究重点在于开发一种优化方法,用于制备载有环丙沙星的白蛋白纳米颗粒(载有CPF的BSA NPs),以有效治疗UPEC及其生物膜。采用去溶剂化方法合成纳米颗粒,并使用两阶段实验设计进行优化。评估参数包括粒径、多分散指数、zeta电位、形态、包封率、药物释放、储存稳定性、细胞毒性以及对UPEC的有效性。优化后的载有CPF的BSA NPs表现出理想的特性,如小粒径(123 nm)、低多分散指数(0.178)、最佳zeta电位(-31.8)和高包封率(> 80%)。它们还表现出低细胞毒性、高稳定性和持续的药物释放,使其成为理想的药物递送系统。至关重要的是,它们对UPEC及其生物膜显示出有效性。本研究表明,使用我们优化的去溶剂化技术合成的优化后的载有CPF的BSA NPs具有有效治疗由UPEC引起的UTIs的潜力。

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