Normandie Université, UNIROUEN, INSA Rouen, CNRS, PBS, 76000 Rouen, France.
Normandie Université, UNIROUEN, INSERM, PRIMACEN, 76000 Rouen, France.
Biomacromolecules. 2021 Apr 12;22(4):1639-1653. doi: 10.1021/acs.biomac.1c00082. Epub 2021 Mar 12.
Conventional antibiotic treatment is in most cases insufficient to eradicate biofilm-related infections, resulting in high risk of treatment failure and recurrent infections. Recent studies have shown that novel methods of antibiotic delivery can improve clinical outcomes and reduce the emergence of antibiotic resistance. The objectives of this work were to develop and evaluate a targeting nanocarrier system that enables effective delivery of antimicrobial drugs to , a commonly virulent human pathogen. For this purpose, we first prepared a formulation of polymeric nanoparticles (NPs) suitable for encapsulation and sustained release of antibiotics. A specific antibody against was used as a targeting ligand and was covalently immobilized onto the surface of nanoparticulate materials. It was demonstrated that the targeting NPs preferentially bound cells and presented an elevated accumulation in the biofilm. Compared to free-form antibiotic, the antibiotic-loaded targeting NPs significantly enhanced bactericidal activity against both in planktonic and biofilm forms. Using a mouse infection model, we observed improved therapeutic efficacy of these antibiotic-loaded NPs after a single intravenous administration. Taken together, our studies show that the targeting nanoparticulate system could be a promising strategy to enhance the biodistribution of antibiotics and thereby improve their efficacy.
在大多数情况下，传统的抗生素治疗不足以消除生物膜相关感染，导致治疗失败和反复感染的风险很高。最近的研究表明，新型抗生素给药方法可以改善临床结果并降低抗生素耐药性的出现。本工作的目的是开发和评估一种靶向纳米载体系统，该系统能够将抗菌药物有效递送至一种常见的人类病原体。为此，我们首先制备了一种适合封装和持续释放抗生素的聚合物纳米颗粒（NP）制剂。针对 的特异性抗体被用作靶向配体，并通过共价键固定在纳米颗粒材料的表面。结果表明，靶向 NP 优先结合 细胞，并在 生物膜中呈现出升高的积累。与游离形式的抗生素相比，负载抗生素的靶向 NP 显著增强了对浮游和生物膜形式的 的杀菌活性。通过小鼠感染模型，我们观察到单次静脉给药后这些载药 NP 的治疗效果得到改善。总之，我们的研究表明，靶向纳米颗粒系统可能是一种有前途的策略，可以提高抗生素的生物分布，从而提高其疗效。
