School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People's Republic of China.
Shenyang Key Laboratory of Chinese Medicine targeted Delivery Key laboratory, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People's Republic of China.
Int J Nanomedicine. 2024 Sep 16;19:9637-9658. doi: 10.2147/IJN.S476471. eCollection 2024.
Resistance of intracellular pathogens is a challenge in microbial therapy. Methicillin-resistant (MRSA), which is able to persist inside the cells of infected tissues, is protected from attack by the immune system and many antimicrobial agents. To overcome these limitations, nano-delivery systems can be used for targeted therapy of intracellular MRSA.
Hyaluronic acid-modified azithromycin/quercetin micelles (HA-AZI/Qe-M) were synthesized by thin film hydration. The micelles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR), and the drug loading (DL) and encapsulation efficiency (EE) were detected by high performance liquid chromatography (HPLC). The uptake ability of RAW264.7 cells was investigated, and its distribution in mice was evaluated by in vivo imaging. The inhibitory effect of the micelles against MRSA in vitro and its ability to eliminate intracellular bacteria were evaluated. Bacterial muscle-infected mice were constructed to evaluate the therapeutic effect of the micelles on bacterial infections in vivo and the biocompatibility of the micelles was investigated.
HA-AZI/Qe-M had suitable physical and chemical properties and characterization. In vitro ntibacterial experiments showed that HA-AZI/Qe-M could effectively inhibit the growth of MRSA, inhibit and eliminate the biofilm formed by MRSA, and have an excellent therapeutic effect on intracellular bacterial infection. The results of RAW264.7 cells uptake and in vivo imaging showed that HA-AZI/Qe-M could increase the cellular uptake, target the infection site, and prolong the treatment time. The results of in vivo antibacterial infection experiments showed that HA-AZI/Qe-M was able to ameliorate the extent of thigh muscle infections in mice and reduce the expression of inflammatory factors.
HA-AZI/Qe-M is a novel and effective nano-drug delivery system that can target intracellular bacterial infection, and it is expected to be safely used for the treatment of MRSA infection.
细胞内病原体的耐药性是微生物治疗的一个挑战。耐甲氧西林金黄色葡萄球菌（MRSA）能够在感染组织的细胞内存活，从而免受免疫系统和许多抗菌药物的攻击。为了克服这些限制，可以使用纳米递药系统对细胞内的 MRSA 进行靶向治疗。
通过薄膜水化法合成了透明质酸修饰的阿奇霉素/槲皮素胶束（HA-AZI/Qe-M）。通过透射电子显微镜（TEM）、动态光散射（DLS）和傅里叶变换红外光谱（FTIR）对胶束进行了表征，并通过高效液相色谱（HPLC）检测了载药量（DL）和包封率（EE）。研究了 RAW264.7 细胞的摄取能力，并通过体内成像评估了其在小鼠体内的分布。评价了胶束对 MRSA 的体外抑制作用及其消除细胞内细菌的能力。构建了细菌肌肉感染小鼠模型，评价了胶束对体内细菌感染的治疗效果，并研究了胶束的生物相容性。
HA-AZI/Qe-M 具有适宜的物理化学性质和表征。体外抗菌实验表明，HA-AZI/Qe-M 能有效抑制 MRSA 的生长，抑制和消除 MRSA 形成的生物膜，对细胞内细菌感染具有极好的治疗效果。RAW264.7 细胞摄取和体内成像的结果表明，HA-AZI/Qe-M 能增加细胞摄取，靶向感染部位，延长治疗时间。体内抗菌感染实验结果表明，HA-AZI/Qe-M 能改善小鼠大腿肌肉感染程度，降低炎症因子的表达。
HA-AZI/Qe-M 是一种新型有效的纳米药物递送系统，能靶向细胞内细菌感染，有望安全用于治疗 MRSA 感染。
