International Journal of Nanomedicine (Nov 2022)
Preparation, Characterization, and Staphylococcus aureus Biofilm Elimination Effect of Baicalein-Loaded β-Cyclodextrin-Grafted Chitosan Nanoparticles
Abstract
Zhongbin Zhang,1,2,* Jinqing Chen,1,* Linghui Zou,1,* Jing Tang,1 Jiaxin Zheng,1 Meijiao Luo,1 Gang Wang,1 Dan Liang,1,2 Yuyang Li,1 Ben Chen,1 Hongjun Yan,1 Wenya Ding1– 3 1Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 2Key Laboratory of Common Technology of Chinese Medicine Preparations, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 3College of Veterinary Medicine, Northeast Agricultural University, Harbin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenya Ding, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China, Tel +86-15045630868, Email [email protected] and Purpose: Infections caused by Staphylococcus aureus (S. aureus) colonization in medical implants are resistant to antibiotics due to the formation of bacterial biofilm internal. Baicalein (BA) has been confirmed as an inhibitor of bacterial biofilm with less pronounced effects owing to its poor solubility and absorption. Studies have found that β-cyclodextrin-grafted chitosan (CD-CS) can improve drug efficiency as a drug carrier. Therefore, this research aims to prepare BA-loaded CD-CS nanoparticles (CD-CS-BA-NPs) for S. aureus biofilm elimination enhancement.Methods: CD-CS-BA-NPs were prepared via the ultrasonic method. The NPs were characterized using the X-ray diffraction (XRD), Thermo gravimetric analyzer (TGA), Transmission electron microscopy (TEM) and Malvern Instrument. The minimum inhibitory concentration (MIC) of the NPs were investigated. The biofilm models in vivo and in vitro were constructed to assess the S. aureus biofilm elimination ability of the NPs. The Confocal laser method (CLSM) and the Live/Dead kit were employed to explore the mechanism of the NPs in promoting biofilm elimination.Results: CD-CS-BA-NPs have an average particle size of 424.5 ± 5.16 nm, a PDI of 0.2 ± 0.02, and a Zeta potential of 46.13 ± 1.62 mV. TEM images revealed that the NPs were spherical with uniform distribution. XRD and TGA analysis verified the formation and the thermal stability of the NPs. The NPs with a MIC of 12.5 ug/mL exhibited a better elimination effect on S. aureus biofilm both in vivo and in vitro. The mechanism study demonstrated that the NPs may permeate into the biofilm more easily, thereby improving the biofilm elimination effect of BA.Conclusion: CD-CS-BA-NPs were successfully prepared with enhanced elimination of S. aureus biofilm, which may serve as a reference for future development of anti-biofilm agents.Graphical Abstract: Keywords: baicalein, β-cyclodextrin-grafted chitosan, nanoparticles, Staphylococcus aureus, biofilm elimination
