Patel Raahi, Moyano Ignacio, Sakagami Masahiro, Kang Jason D, Hylemon Phillip B, Voynow Judith A, Heise Rebecca L
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23219, USA.
Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23219, USA.
Int J Mol Sci. 2025 Aug 1;26(15):7453. doi: 10.3390/ijms26157453.
Cystic fibrosis produces viscous mucus in the lung that increases bacterial invasion, causing persistent infections and subsequent inflammation. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most common infections in cystic fibrosis patients that are resistant to antibiotics. One antibiotic approved to treat these infections is levofloxacin (LVX), which functions to inhibit bacterial replication but can be further developed into tailorable particles. Nanoparticles are an emerging inhaled therapy due to enhanced targeting and delivery. The extracellular matrix (ECM) has been shown to possess pro-regenerative and non-toxic properties in vitro, making it a promising delivery agent. The combination of LVX and ECM formed into nanoparticles may overcome barriers to lung delivery to effectively treat cystic fibrosis bacterial infections. Our goal is to advance CF care by providing a combined treatment option that has the potential to address both bacterial infections and lung damage. Two hybrid formulations of a 10:1 and 1:1 ratio of LVX to ECM have shown neutral surface charges and an average size of ~525 nm and ~300 nm, respectively. The neutral charge and size of the particles may suggest their ability to attract toward and penetrate through the mucus barrier in order to target the bacteria. The NPs have also been shown to slow the drug dissolution, are non-toxic to human airway epithelial cells, and are effective in inhibiting and . LVX-ECM NPs may be an effective treatment for pulmonary CF bacterial treatments.
囊性纤维化会在肺部产生黏稠的黏液，增加细菌入侵，导致持续性感染及随后的炎症。铜绿假单胞菌和金黄色葡萄球菌是囊性纤维化患者中最常见的两种对抗生素耐药的感染源。一种被批准用于治疗这些感染的抗生素是左氧氟沙星（LVX），它的作用是抑制细菌复制，但可以进一步开发成可定制的颗粒。纳米颗粒由于靶向性和递送能力增强，成为一种新兴的吸入疗法。细胞外基质（ECM）在体外已显示出具有促再生和无毒特性，使其成为一种有前景的递送载体。将LVX和ECM制成纳米颗粒的组合可能会克服肺部递送的障碍，从而有效治疗囊性纤维化细菌感染。我们的目标是通过提供一种有可能同时解决细菌感染和肺部损伤问题的联合治疗方案来推进囊性纤维化的治疗。两种LVX与ECM比例为10:1和1:1的混合制剂分别显示出中性表面电荷，平均粒径分别约为525纳米和300纳米。颗粒的中性电荷和大小可能表明它们有能力吸引并穿透黏液屏障以靶向细菌。这些纳米颗粒还显示出能减缓药物溶解，对人气道上皮细胞无毒，并且在抑制……方面有效。LVX - ECM纳米颗粒可能是治疗肺部囊性纤维化细菌感染的有效方法。
