scholarly journals A Synergistic Bactericidal Effect of Low-Frequency and Low-Intensity Ultrasound Combined with Levofloxacin-Loaded PLGA Nanoparticles on M. Smegmatis in Macrophages

2020 ◽  
Author(s):  
Shuang Xie ◽  
Gangjing Li ◽  
Yuru Hou ◽  
Min Yang ◽  
Fahui Li ◽  
...  

Abstract Purpose: Tuberculosis (TB) is a highly infectious disease caused by Mycobacterium tuberculosis (Mtb), which often parasites in macrophages. This study is performed to investigate the bactericidal effect and underlying mechanisms of low-frequency and low-intensity ultrasound (LFLIU) combined with levofloxacin-loaded PLGA nanoparticles (LEV-NPs) on M. smegmatis (a surrogate of Mtb) in macrophages.Methods and results: The LEV-NPs were prepared using a double emulsification method. The average diameter, zeta potential, polydispersity index, morphology, and drug release efficiency in vitro of the LEV-NPs were investigated. M. smegmatis in macrophages was treated using the LEV-NPs combined with 42 kHz ultrasound irradiation at an intensity of 0.13 W/cm2 for 10 min. The results showed that ultrasound significantly promoted the phagocytosis of nanoparticles by macrophages (p < 0.05). In addition, further ultrasound combined with the LEV-NPs promoted the production of reactive oxygen species (ROS) in macrophage , and the apoptosis rate of the macrophages was significantly higher than that of the control (p < 0.05). The transmission electronic microscope showed that the cell wall of M. smegmatis was ruptured, the cell structure was incomplete, and the bacteria received severe damage in the ultrasound combined with the LEV-NPs group. Activity assays showed that ultrasound combined with the LEV-NPs exhibited a 10-fold higher antibacterial activity against M. smegmatis residing inside macrophages compared with the free drug.Conclusion: These data demonstrated that ultrasound combined with LEV-NPs has great potential as a therapeutic agent for TB.

2020 ◽  
Author(s):  
Shuang Xie ◽  
Gangjing Li ◽  
Yuru Hou ◽  
Min Yang ◽  
Fahui Li ◽  
...  

Abstract Purpose: Tuberculosis (TB) is a highly infectious disease caused by Mycobacterium tuberculosis (Mtb), which often parasites in macrophages. This study is performed to investigate the bactericidal effect and underlying mechanisms of low-frequency and low-intensity ultrasound (LFLIU) combined with levofloxacin-loaded PLGA nanoparticles (LEV-NPs) on M. smegmatis (a surrogate of Mtb) in macrophages.Methods and results: The LEV-NPs were prepared using a double emulsification method. The average diameter, zeta potential, polydispersity index, morphology, and drug release efficiency in vitro of the LEV-NPs were investigated. M. smegmatis in macrophages was treated using the LEV-NPs combined with 42 kHz ultrasound irradiation at an intensity of 0.13 W/cm2 for 10 min. The results showed that ultrasound significantly promoted the phagocytosis of nanoparticles by macrophages (p < 0.05). In addition, further ultrasound combined with the LEV-NPs promoted the production of reactive oxygen species (ROS) in macrophage, and the apoptosis rate of the macrophages was significantly higher than that of the control (p < 0.05). The transmission electronic microscope showed that the cell wall of M. smegmatis was ruptured, the cell structure was incomplete, and the bacteria received severe damage in the ultrasound combined with the LEV-NPs group. Activity assays showed that ultrasound combined with the LEV-NPs exhibited a 10-fold higher antibacterial activity against M. smegmatis residing inside macrophages compared with the free drug.Conclusion: These data demonstrated that ultrasound combined with LEV-NPs has great potential as a therapeutic agent for TB.


2020 ◽  
Author(s):  
Shuang Xie ◽  
Gangjing Li ◽  
Yuru Hou ◽  
Min Yang ◽  
Fahui Li ◽  
...  

Abstract Purpose Tuberculosis is a highly infectious disease caused by Mycobacterium tuberculosis (Mtb) which often parasites in macrophages. The present study was to investigate the bactericidal effect and underlying mechanisms of low-frequency and low-intensity ultrasound (LFLIU) combined with levofloxacin-loaded nanoparticles (LEV-NPs) on M. smegmatis (a surrogate of Mtb )in macrophages. Methods and results LEV-NPs were prepared by a double emulsification method. The characterization, such as average diameter, zeta potential, polydispersity index and morphology, and in-vitro drug release efficiency of LEV-NPs were investigated. M. smegmatis in macrophages was treated by LEV-NPs combined with 42 kHz ultrasound irradiation at an intensity of 0.13 W/cm 2 for 10 min. The results showed ultrasound could significantly promote phagocytosis of nanoparticles by macrophages ( p <0.05), further ultrasound combined with LEV-NPs could promote the production of macrophage ROS, and the apoptosis rate of macrophages was significantly higher than that of the control ( p <0.05). Transmission electronic microscope showed M. smegmatis cell wall was ruptured, the cell structure was incomplete, and the bacteria received severe damage in the ultrasound combined with the LEV-NPs group. Activity assays showed that ultrasound combined with LEV-NPs exhibited 10-fold higher antibacterial activity against M. smegmatis residing inside macrophages compared with free drug. Conclusion Our data demonstrate that ultrasound combined with LEV-NPs have a great potential to therapy of tuberculosis.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xiaofei Qi ◽  
Kexin Lyu ◽  
Long Meng ◽  
Cuixian Li ◽  
Hongzheng Zhang ◽  
...  

Cochlear implantation is the first-line treatment for severe and profound hearing loss in children and adults. However, deaf patients with cochlear malformations or with cochlear nerve deficiencies are ineligible for cochlear implants. Meanwhile, the limited spatial selectivity and high risk of invasive craniotomy restrict the wide application of auditory brainstem implants. A noninvasive alternative strategy for safe and effective neuronal stimulation is urgently needed to address this issue. Because of its advantage in neural modulation over electrical stimulation, low-intensity ultrasound (US) is considered a safe modality for eliciting neural activity in the central auditory system. Although the neural modulation ability of low-intensity US has been demonstrated in the human primary somatosensory cortex and primary visual cortex, whether low-intensity US can directly activate auditory cortical neurons is still a topic of debate. To clarify the direct effects on auditory neurons, in the present study, we employed low-intensity US to stimulate auditory cortical neurons in vitro. Our data show that both low-frequency (0.8 MHz) and high-frequency (>27 MHz) US stimulation can elicit the inward current and action potentials in cultured neurons. c-Fos staining results indicate that low-intensity US is efficient for stimulating most neurons. Our study suggests that low-intensity US can excite auditory cortical neurons directly, implying that US-induced neural modulation can be a potential approach for activating the auditory cortex of deaf patients.


2018 ◽  
Author(s):  
Min Yang ◽  
Kaiyue Du ◽  
Yuru Hou ◽  
Shuang Xie ◽  
Yu Dong ◽  
...  

AbstractC. albicans is human opportunistic pathogens that cause superficial and life-threatening infections. An important reason for the failure of current antifungal drugs is related to biofilm formation mostly associated with implanted medical device. The present study aims to investigate the synergistic antifungal efficacy of low-frequency and low-intensity ultrasound combined with amphotericin B-loaded PLGA nanoparticles (AmB-NPs) on C.albicans biofilms. AmB-NPs were prepared by a double emulsion method and demonstrated the lower toxicity than free AmB, after which biofilms were established and treated with ultrasound and AmB-NPs separately or jointly in vitro and in vivo. The results demonstrated the activity, biomass, and proteinase and phospholipase activities of biofilms were decreased significantly after the combination treatment of AmB-NPs with 42 KHz ultrasound irradiation at an intensity of 0.30 W/cm2 for 15 min compared to the control, the AmB alone or the ultrasound alone treatment (P < 0.01), and the morphology of biofilms was altered remarkably after jointly treatment under CLSM observation and detection, especially thickness thinning and structure loosing. Furthermore, the same synergistic effects were proved in a subcutaneous catheter biofilm rat model. The result of colony forming units of catheter fungus loading exhibited a significant reduction after AmB-NPs and ultrasound jointly treatment for 7 days continuous therapy, and the CLSM images revealed that the biofilm on the catheter surface was substantially eliminated. Our study may provide a new noninvasive, safe and effective application to C.albicans biofilm infection therapy.


2021 ◽  
Vol 17 (10) ◽  
pp. 1939-1950
Author(s):  
Beibei Lin ◽  
Xuegu Xu ◽  
Xiaobi Zhang ◽  
Yinfei Yu ◽  
Xiaoling Wang

We prepared poly(lactide-co-glycolide) (PLGA) encapsulated with chlorin e6 (Ce6) in an effort to increase the stability and efficiency of photosensitizers for photodynamic therapy (PDT). We determined that Ce6-loaded PLGA nanoparticles (PLGA-Ce6 NPs) had drug-loading efficiency of 5%. The efficiency of encapsulation was 82%, the zeta potential was- 25 mV, and the average diameter was 130 nm. The encapsulation of Ce6 in PLGA nanoparticles showed excellent stability. The nanoparticles exhibited sustained Ce6 release profiles with 50% released at the end of 3 days, whereas free Ce6 showed rapid release within 1 day. Ce6 release patterns were controlled by encapsulation into PLGA. The uptake of PLGA-Ce6 NPs was significantly enhanced by endocytosis in the first 8 hours in the HCT-116 cell line. An intracellular reactive oxygen species assay revealed the enhanced uptake of the nanoparticles. An in vitro anti-tumor activity assay showed that the PLGA-Ce6 NPs exhibited enhanced phototoxicity toward HCT-116 cells and a slightly lower IC50 value in HCT-116 cells than Ce6 solution alone. Exposure of HCT-116 cell spheroids to PLGA-Ce6 NPs penetrated more profoundly and had better phototoxicity than pure drugs. These findings suggest that PLGA-Ce6 NPs might serve as PDT for colorectal cancer.


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