Sangboonruang Sirikwan, Semakul Natthawat, Poomanee Worrapan, Thavanapong Thasang, Roytrakul Sittiruk, Charoenlappanit Sawanya, Thaisakun Siriwan, Khantipongse Jiaranai, Netirat Nathiprada, Tongsong Apiwadee, Wattananandkul Usanee, Intorasoot Sorasak, Phunpae Ponrut, Tragoolpua Khajornsak
Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
Infectious Diseases Research Unit (IDRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
Sci Rep. 2025 May 30;15(1):19029. doi: 10.1038/s41598-025-04673-2.
Tuberculosis (TB) treatment faces significant challenges due to prolonged therapy and drug resistance, necessitating innovative anti-TB strategies. Thus, developing an innovative platform with effective anti-TB activity would offer more advantages. In this study, the pH-sensitive niosomal formulation of lactoferricin (Lfcin-Nio) was fabricated using a microfluidic system. The optimization of Lfcin-Nio formulation was statistically carried out based on the Central Composite Design (CCD). The desirable properties of Lfcin-Nio were achieved with a small particle size (171.68 ± 0.97 nm), a narrow polydispersity index; PDI (0.24 ± 0.002), an acceptable zeta potential; ZP (- 69.86 ± 0.64 mV), and high entrapment efficiency; %EE (75.59 ± 2.78%) with a prediction error of less than 5%. Lfcin-Nio demonstrated low cytotoxicity and stability for 28 days at room temperature and 4 °C. Lfcin-Nio also had a release profile in response to acidic pH, with approximately 50%, 70%, and 80% cumulative release at pH 7.4, 6.5, and 5.5, respectively, within the first 6 h. Notably, Lfcin-Nio exhibited enhanced anti-mycobacterial activity against both extracellular and intracellular Mycobacterium tuberculosis (Mtb), requiring a lower concentration for intracellular Mtb attenuation. Proteomic analysis revealed that Lfcin-Nio modulated immune response-related proteins, including complement C6 activation and suppression of inflammatory mediators. These findings suggest that Lfcin-Nio represents a promising anti-TB agent and further applies as a potential advancement in TB therapy.
由于治疗时间长和耐药性问题，结核病（TB）治疗面临重大挑战，因此需要创新的抗结核策略。因此，开发具有有效抗结核活性的创新平台将具有更多优势。在本研究中，使用微流控系统制备了乳铁蛋白（Lfcin-Nio）的pH敏感脂质体剂型。基于中心复合设计（CCD）对Lfcin-Nio剂型进行了统计学优化。Lfcin-Nio具有小粒径（171.68±0.97nm）、窄多分散指数；PDI（0.24±0.002）、可接受的zeta电位；ZP（-69.86±0.64mV）和高包封率；%EE（75.59±2.78%），预测误差小于5%等理想特性。Lfcin-Nio在室温及4℃下表现出低细胞毒性和28天的稳定性。Lfcin-Nio在酸性pH值下也有释放曲线，在最初6小时内，在pH 7.4、6.5和5.5时的累积释放率分别约为50%、70%和80%。值得注意的是，Lfcin-Nio对细胞外和细胞内结核分枝杆菌（Mtb）均表现出增强的抗分枝杆菌活性，细胞内Mtb衰减所需浓度较低。蛋白质组学分析表明，Lfcin-Nio调节免疫反应相关蛋白，包括补体C6激活和炎症介质抑制。这些发现表明Lfcin-Nio是一种有前景的抗结核药物，并可作为结核病治疗的潜在进展进一步应用。
