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用于结核病治疗的主动靶向金-聚多巴胺纳米颗粒制剂的研发、表征及抗菌疗效评估

Development, characterization and evaluation of antibacterial efficacy of actively targeted gold-polydopamine nanoparticle formulations for tuberculosis treatment.

作者信息

Turan-Ayhan Eda, Çalımcı Merve, Turanlı Yasin, Şahin Funda, Tarhan Gülnur, Tamer Ugur, Ilbasmis-Tamer Sibel

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmacy, Gazi University, Ankara, Türkiye; Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Adıyaman University, Adıyaman, Türkiye.

Department of Analytical Chemistry, Faculty of Pharmacy, Gazi University, Ankara, Türkiye.

出版信息

Eur J Pharm Sci. 2025 Oct 1;213:107219. doi: 10.1016/j.ejps.2025.107219. Epub 2025 Aug 7.

DOI:10.1016/j.ejps.2025.107219
PMID:40754012
Abstract

Tuberculosis (TB) is one of the oldest known diseases in the world and it remains a significant public health challenge. The increasing resistance of microorganisms to antibiotics underlines the necessity of appropriate use of antibiotics and correct dosage in treatment. In some cases, frequent and high-dose drug therapy is required, which can lead to serious organ damage in the liver and kidneys in long-term treatment. However, this problem can be overcome by using appropriate drug delivery systems that allow more effective treatments at lower doses. Here, we developed a drug delivery system specifically targeting tuberculosis using gold (Au)-polydopamine (PDA) nanoparticles and modified with polyethylene glycol (PEG), a targeting agent (antibody), and the antibiotic linezolid, resulting in Au-PDA-PEG-Antibody-Linezolid nanoparticles. We successfully developed and characterized these active targeted nanoparticles using UV-Vis absorbance spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), zeta potential measurements, and surface-enhanced Raman spectroscopy (SERS) measurements. Additionally, the developed formulations were compared with the commercial product through in vitro release studies, and antibacterial efficacy studies were conducted on multidrug-resistant tuberculosis (MDR-TB) strains. The targeted drug delivery system might be able to reduce side effects by increasing treatment effectiveness at lower doses. Additionally, our study is the one of the first example to feature actively targeted nanoparticle formulations using the active ingredient linezolid and PEGs with different chemical structures.

摘要

结核病是世界上已知最古老的疾病之一,至今仍是一项重大的公共卫生挑战。微生物对抗生素的耐药性不断增加,凸显了治疗中合理使用抗生素及正确剂量的必要性。在某些情况下,需要频繁且高剂量的药物治疗,长期治疗可能会导致肝脏和肾脏等重要器官受损。然而,通过使用合适的药物递送系统,以较低剂量实现更有效的治疗,这个问题是可以克服的。在此,我们利用金(Au)-聚多巴胺(PDA)纳米颗粒,并结合聚乙二醇(PEG)、靶向剂(抗体)和抗生素利奈唑胺,开发了一种专门针对结核病的药物递送系统,即Au-PDA-PEG-抗体-利奈唑胺纳米颗粒。我们通过紫外可见吸收光谱、傅里叶变换红外光谱(FT-IR)、动态光散射(DLS)、zeta电位测量和表面增强拉曼光谱(SERS)测量,成功地开发并表征了这些主动靶向纳米颗粒。此外,通过体外释放研究将所开发的制剂与市售产品进行了比较,并对耐多药结核(MDR-TB)菌株进行了抗菌疗效研究。这种靶向药物递送系统或许能够通过在较低剂量下提高治疗效果来减少副作用。此外,我们的研究是首批使用活性成分利奈唑胺和具有不同化学结构的聚乙二醇的主动靶向纳米颗粒制剂的实例之一。

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