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CELL BIOCHEMISTRY AND BIOPHYSICS · 2023 · IF 2.6

Exploring Different Ultrasonic Parameters and Treatment Conditions to Optimize In Vitro Sonodynamic Therapeutic Effects in Cancer Cells

Zheng Yilin,Wang Jun,Chen Haijun,Gao Yu

The effects of ultrasonic parameters and treatment conditions on the in vitro cellular experiments of sonodynamic therapy (SDT) have not been fully studied. Exploring the factors that affect the efficacy of SDT can provide a reference for screening effective sonosensitizers in vitro. The aim of this work is to investigate the factors that affected the SDT effects in cancer cells. Cancer cells in culture plates were exposed to ultrasound and sonosensitizers. The intracellular drug concentration was measured by using flow cytometry and the cell viability was determined by MTT assay. The SDT effects of cancer cells treated with different ultrasonic parameters under the same sonosensitizer concentration were different. The ultrasonic parameters, intracellular drug concentration, drug treatment time, cell amount, and cell status could affect the sonodynamic therapeutic effects. It is necessary to select appropriate ultrasound conditions and optimize the cellular status to make the results of the in vitro cellular experiments more reliable.

CAS / MDL: 3599-32-4
研究领域: 肿瘤学 · 生物医学工程 · 细胞生物学
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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH · 2023 · IF 4.2

Ultrasound Emulsification in Microreactors: Effects of Channel Material, Surfactant Nature, and Ultrasound Parameters

Shuainan Zhao,Chaoqun Yao,Lixue Liu,Mei Yang,Guangwen Chen

Ultrasound emulsification, including the emulsification mechanism as well as the stability and size distribution of the prepared emulsion, was systematically investigated in laboratory-built ultrasonic microreactors. The respective cavitation-induced emulsification processes in hydrophilic and hydrophobic microchannels were first analyzed, after which a bubble shuttling and dispersing mechanism was proposed. The type of prepared emulsion was found to be strongly associated with the hydrophilic–lipophilic balance (HLB) value and water/oil ratio of the emulsified system, but was hardly affected by the ultrasound parameters. The size distribution of the prepared emulsion was characterized using both microscopy and dynamic scattering technique, and was measured to be in the range of 700–1800 nm. It was also found that higher ultrasound intensity, lower frequency, and larger residence time are more favorable to producing fine emulsion. Finally, an operation strategy was proposed on the basis of the experimental results, expecting to provide recommendations for the application of ultrasonic microreactors for continuous emulsification.

研究领域: 化学工程 · 材料科学 · 生物技术
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PHYSICS IN MEDICINE AND BIOLOGY · 2022 ·Vol. 67 ·期 19 ·195005 · IF 4.174

Parameter effects on arterial vessel sonicated by high-intensity focused ultrasound: an ex vivo vascular phantom study

Qianwen Huang,Yun Zhou,Ke Li,Lei Pan,Yuan Liu,Jingfeng Bai,Xiang Ji

Objective. This study is aimed to explore the effects of vascular and sonication parameters on ex vivo vessel sonicated by high-intensity focused ultrasound. Approach. The vascular phantom embedding the polyolefin tube or ex vivo vessel was sonicated. The vascular phantom with 1.6 and 3.2 mm tubes was sonicated at three acoustic powers (2.0, 3.5, 5.3 W). The occlusion level of post-sonication tubes was evaluated using ultrasound imaging. The vascular phantom with the ex vivo abdominal aorta of rabbit for three flow rates (0, 5, 10 cm s−1) was sonicated at two acoustic powers (3.5 and 5.3 W). Different distances between focus and posterior wall (2, 4, 6 mm) and cooling times (0 and 10 s) were also evaluated. The diameter of the sonicated vessel was measured by B-mode imaging and microscopic photography. Histological examination was performed for the sonicated vessels. Main results. For the 5 cm s−1 flow rate, the contraction index of vascular diameter (Dc) with 5.3 W and 10 s cooling time at 2 mm distance was 39 ± 9% (n = 9). With the same parameters except for 0 cm s−1 flow rate, the Dc was increased to 45 ± 7% (n = 4). At 3.5 W, the Dc with 5 cm s−1 flow rate was 23 ± 15% (n = 4). The distance and cooling time influenced the lesion along the vessel wall. Significance. This study has demonstrated the flow rate and acoustic power have the great impact on the vessel contraction. Besides, the larger lesion covering the vessel wall would promote the vessel contraction. And the in vivo validation is required in the future study.

CAS / MDL: 110-18-9
研究领域: 生物医学工程 · 超声技术 · 血管研究
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SEPARATION AND PURIFICATION TECHNOLOGY · 2014 · IF 3.065

Control the effects caused by noise parameter fluctuations to improve pharmaceutical process robustness: A case study of design space development for an ethanol precipitation process

Xingchu Gong,Yao Li,Zhengtai Guo,Haibin Qu

To provide a new method to develop a design space to improve the robustness of drug manufacturing processes based on the control of noise parameter influences, the ethanol precipitation process of Danhong injection was investigated as a sample. Water content in the concentrated extract (WCCE), the concentration of ethanol (CEA), and the amount of ethanol added (AEA) are three adjustable parameters. The effects of refrigeration temperature (RT) was investigated on three levels for simulating its fluctuations. The models between parameters and process critical quality attributes (CQAs) were obtained using a simplified central composite design with determination coefficients more than 0.84. The decrease of RT led to lower active ingredient recoveries and higher DMR. The increase of CEA and the decrease of WCCE caused more precipitation. The decrease of CEA or AEA resulted in higher active ingredient recoveries. The design space was calculated using an exhaustive search-Monte Carlo method and normal operation ranges were also obtained. The results of verification experiments agreed well with prediction results. The proposed method can be used to develop a design space applicable in a larger scale manufacturing process with the negative effects caused by the fluctuations of noise parameters controlled.

CAS / MDL: 78281-02-4
研究领域: 制药工程 · 生物技术
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2023 · IF 5.8

Application of low-intensity ultrasound by opening blood–brain barrier for enhanced brain-targeted drug delivery

Qian Li,Ziyan Tang,Yuanyuan Zhang,Tianyu Yuan,Bochuan Yuan,Lina Du,Yiguang Jin

Brain-targeted drug delivery has been a research hotspot, and substantial amount of related studies were already translated into standard therapy and put into clinical use. However, low effective rate retains a huge challenge for brain disease. Because, the blood–brain barrier (BBB) protects brain from pathogenic molecules and tightly controls the process of molecular transportation, which gives rise to poor-liposoluble drugs or molecules with high molecular weight cannot permeate the barrier to exert treating effect. There is an ongoing process to dig out more methods for efficient brain-targeted drug delivery. Besides modified chemical methods such as prodrugs design and brain-targeted nanotechnology, physical methods as a novel initiative could enhance the treatment effect for brain disease. In our study, the influence of low-intensity ultrasound on transient opening BBB and the related applications were explored. A medical ultrasound therapeutic device (1 MHz) was used on heads of mice at different intensities and for different treating time. Evans blue was used as a model to exhibit the permeability of the BBB after subcutaneous injection . Three types of intensities (0.6, 0.8, and 1.0 W/cm 2 ) and duration times (1, 3, and 5 min) of ultrasound were respectively investigated. It was found that the combinations of 0.6 W/cm 2 /1 min, 0.6 W/cm 2 /3 min, 0.6 W/cm 2 /5 min, 0.8 W/cm 2 /1 min, and 1.0 W/cm 2 /1 min could open the BBB sufficiently with significant Evans blue staining in the brain. Brain pathological analysis showed structural change on moderate degree was found on cerebral cortex after ultrasound and could recovered rapidly. There are no obvious changes in the behavior of mice after ultrasound processing. More importantly, the BBB recovered quickly at 12 h after ultrasound application with complete BBB structure and unbroken tight junction, suggesting that ultrasound was safe to apply for brain-targeted drug delivery. Proper use of local ultrasound on the brain is a promising technique to open the BBB and enhance brain-targeted delivery.

CAS / MDL: 75-12-7
研究领域: 神经科学 · 药理学 · 治疗技术
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