Hyaluronic Acid-Modified Micelles of Azithromycin and Quercetin Against Infections Caused by Methicillin-Resistant Staphylococcus Aureus

被引:5
作者
Zhang, Zixu [1 ,2 ]
Chen, Muhan [1 ,2 ]
Wang, Jiahua [1 ,2 ]
Liu, Mo [1 ,2 ]
Guo, Ruibo [1 ,2 ]
Zhang, Lu [1 ,2 ]
Kong, Liang [1 ,2 ]
Liu, Yang [1 ,2 ]
Yu, Yang [1 ,3 ]
Li, Xuetao [1 ,2 ]
机构
[1] Liaoning Univ Tradit Chinese Med, Sch Pharm, Dalian 116600, Peoples R China
[2] Liaoning Univ Tradit Chinese Med, Shenyang Key Lab Chinese Med Targeted Delivery, Key Lab, Shenyang 110847, Peoples R China
[3] Liaoning Univ Tradit Chinese Med, Key Lab, Minist Educ TCM Viscera State Theory & Applicat, Shenyang, Peoples R China
基金
中国博士后科学基金;
关键词
MRSA; hyaluronic acid; antibiotics; micelles; azithromycin; quercetin; BIOFILM FORMATION; CELLULAR UPTAKE; DRUG-DELIVERY; CO-DELIVERY; ANTIBACTERIAL; QUANTIFICATION; NANOPARTICLES; MECHANISMS;
D O I
10.2147/IJN.S476471
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Introduction: Resistance of intracellular pathogens is a challenge in microbial therapy. Methicillin-resistant Staphylococcus aureus (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. Methods: 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. Results: HA-AZI/Qe-M had suitable physical and chemical properties and characterization. In vitro antibacterial 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. Conclusion: 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.
引用
收藏
页码:9637 / 9658
页数:22
相关论文
共 85 条
[1]   Nanoparticles: Cellular Uptake and Cytotoxicity [J].
Adjei, Isaac M. ;
Sharma, Blanka ;
Labhasetwar, Vinod .
NANOMATERIAL: IMPACTS ON CELL BIOLOGY AND MEDICINE, 2014, 811 :73-91
[2]   Emergent crisis of antibiotic resistance: A silent pandemic threat to 21st century [J].
Akram, Fatima ;
Imtiaz, Memoona ;
ul Haq, Ikram .
MICROBIAL PATHOGENESIS, 2023, 174
[3]   Factors affecting the clearance and biodistribution of polymeric nanoparticles [J].
Alexis, Frank ;
Pridgen, Eric ;
Molnar, Linda K. ;
Farokhzad, Omid C. .
MOLECULAR PHARMACEUTICS, 2008, 5 (04) :505-515
[4]   Safety Assessment of Nanomaterials for Antimicrobial Applications [J].
Ali, Arbab ;
Ovais, Muhammad ;
Cui, Xuejing ;
Rui, Yukui ;
Chen, Chunying .
CHEMICAL RESEARCH IN TOXICOLOGY, 2020, 33 (05) :1082-1109
[5]   Recent advancement, immune responses, and mechanism of action of various vaccines against intracellular bacterial infections [J].
Ali, Asmat ;
Waris, Abdul ;
Khan, Muhammad Ajmal ;
Asim, Muhammad ;
Khan, Atta Ullah ;
Khan, Sahrish ;
Zeb, Jehan .
LIFE SCIENCES, 2023, 314
[6]   Quercetin derivatives: Drug design, development, and biological activities, a review [J].
Alizadeh, Seyedeh Roya ;
Ebrahimzadeh, Mohammad Ali .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2022, 229
[7]   Doxorubicin-loaded micelles in tumor cell-specific chemotherapy [J].
Almajidi, Yasir Qasim ;
Kadhim, Mustafa M. ;
Alsaikhan, Fahad ;
Jalil, Abduladheem Turki ;
Sayyid, Nidhal Hassan ;
Ramirez-Coronel, Andres Alexis ;
Jawhar, Zanko Hassan ;
Gupta, Jitendra ;
Nabavi, Noushin ;
Yu, Wei ;
Ertas, Yavuz Nuri .
ENVIRONMENTAL RESEARCH, 2023, 227
[8]   The Role of Nanoparticles in the Inhibition of Multidrug-Resistant Bacteria and Biofilms [J].
AlMatar, Manaf ;
Makky, Essam A. ;
Var, Isil ;
Koksal, Fatih .
CURRENT DRUG DELIVERY, 2018, 15 (04) :470-484
[9]   Micellar Drug Delivery Systems Based on Natural Biopolymers [J].
Atanase, Leonard Ionut .
POLYMERS, 2021, 13 (03) :1-33
[10]  
Beutler B, 2002, Wien Med Wochenschr, V152, P547, DOI 10.1046/j.1563-258X.2002.02097.x