Preparation and In Vitro Evaluation of a Nano Ultrasound Contrast Agent Targeting Pancreatic Cancer

2021 ◽  
Vol 21 (3) ◽  
pp. 1413-1418
Author(s):  
Wu Chen ◽  
Xiaofang Liu ◽  
Yiying Li ◽  
Yongsheng Yang ◽  
Kun Xu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Particle Size ◽  
Contrast Agent ◽  
Drug Loading ◽  
Ultrasound Contrast Agent ◽  
Ultrasound Contrast ◽  
Loading Efficiency ◽  
Targeted Ultrasound ◽  
Drug Loading Efficiency

To prepare a nano-sized ultrasound contrast agent that specifically targets pancreatic cancer cells and to evaluate its targeting effect In Vitro. PLGA-PEG-NHS was synthesized using PLGA, NHS, and PEG and detected using 1H-NMR. PLGA-PEG-NHS and PFOB were used to prepare PLGA nano contrast agent coated with PFOB by emulsification and volatilization, and then a hedgehog antibody was conjugated. The morphology of the nano contrast agent was observed using a transmission electron microscope, and its particle size and potential were measured using the dynamic light scattering method. The entrapment and drug loading efficiency of the nano contrast agent was measured using gas chromatography-mass spectrometry. The In Vitro release characteristics of the nano contrast agent was measured using the dialysis method. Human pancreatic cancer cell lines SW1990 and CFPAC1 were cultured in medium containing the nano contrast agent. The targeting ability of the nano contrast agent was qualitatively and quantitatively verified using fluorescence microscopy and flow cytometry. The average particle size of the targeted ultrasound contrast agent was 198.9 nm, zeta potential was −31.8 mv, entrapment rate was 63.7±3.9%, drug loading efficiency was 14.3±0.9%, and drug release was 85.3% in 48 h. In Vitro cell experiments showed that the targeted ultrasound contrast agent strongly bound to SW1990 cells with high expression of hedgehog antigen, but no specific binding was detected in CFPAC-1 cells which lack the hedgehog antigen. The nano ultrasound contrast agent prepared by emulsification and volatilization method can be potentially used for the diagnosis of pancreatic cancer.

In Vitro Evaluation of Ultrasound-Assisted Thrombolysis Using a Targeted Ultrasound Contrast Agent

2009 ◽  
Vol 31 (4) ◽  
pp. 235-246 ◽  
Author(s):  
Szu-Chia Chen ◽  
Jia-Ling Ruan ◽  
Po-Wen Cheng ◽  
Yueh-Hsun Chuang ◽  
Pai-Chi Li
Keyword(s):  
Contrast Agent ◽  
Weight Reduction ◽  
Ultrasound Contrast Agent ◽  
High Frequency Ultrasound ◽  
Ultrasound Frequency ◽  
Ultrasound Contrast ◽  
Targeted Ultrasound ◽  
Targeted Microbubbles ◽  
Ultrasound Assisted

A thrombus-targeted ultrasound contrast agent bound with tirofiban — a glycoprotein (GP) IIb/IIIa antagonist that can specifically bind to activated platelets in the thrombus — was designed to enhance both the image contrast and thrombolysis effect. In this study, we used 76 canine thrombi for investigation. The targeting ability to thrombi was confirmed by microphotography and high-frequency ultrasound (40 MHz) imaging. The effect of the targeted microbubbles on thrombolysis enhancement was investigated using an in vitro flow system: targeted and nontargeted microbubbles flowed through the clot for 30 seconds with a washing step; the microbubbles remained on the clot that were then cavitated by ultrasound (frequency = 1 MHz, MI = 1.2). The extent of thrombolysis was evaluated by weight reduction and histology analysis. The targeted microbubbles reduced the weight of thrombi by a factor of 1.7 times that of the nontargeted microbubbles. (clot weight reduction: 23.1 ± 5.3% versus 13.6 ± 4.9%, p < 0.01 between targeted and nontargeted group), and the signal enhancement was 3.34 ± 0.30 dB (mean ± SD, p < 0.01 compared to control). We conclude that targeted microbubbles are applicable not only for molecular imaging of thrombi but also for improving the effectiveness of ultrasound-assisted thrombolysis.

A novel dual-targeted ultrasound contrast agent provides improvement of gene delivery efficiency in vitro

Tumor Biology ◽  
2016 ◽  
Vol 37 (7) ◽  
pp. 8609-8619 ◽  
Author(s):  
Jinfeng Xu ◽  
Xinxin Zeng ◽  
Yingying Liu ◽  
Hui Luo ◽  
Zhanghong Wei ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Contrast Agent ◽  
Ultrasound Contrast Agent ◽  
Ultrasound Contrast ◽  
Targeted Ultrasound ◽  
Delivery Efficiency

scholarly journals Preparation of anti-HER-2 antibody PLGA polymer nano- ultrasound contrast agent In vitro targeting experiment

2019 ◽  
Author(s):  
Ji Lin ◽  
Molly Stevens ◽  
John Smith
Keyword(s):  
Breast Cancer ◽  
Particle Size ◽  
Electron Microscope ◽  
Contrast Agent ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Ultrasound Contrast Agent ◽  
Ultrasound Contrast ◽  
Her 2

AbstractIn this report, we demonstrated a novel method to prepare a hollow nano-targeted ultrasound contrast agent carrying anti-HER-2 antibody with high molecular weight polylactic acid-glycolic acid (PLGA) as a film-forming material, and to investigate in vitro targeting and imaging effects. We utilized the camphor as porogen, PLGA nano-ultrasound contrast agent was prepared by modified double emulsion solvent evaporation method. The general characteristics were characterized by scanning electron microscope, transmission electron microscope and laser particle size analyzer. The angiography was performed by carbodiimide method. The anti-HER-2 antibody was used to prepare the PLGA-targeted nano-ultrasound contrast agent with anti-HER-2 antibody. The in-situ imaging ability was evaluated by laser confocal scanning microscopy. Results indicate that the average particle size of PLGA nano-ultrasound contrast agent was (152.00± 58.08) nm. The particles were regular spherical, uniform in size and good in dispersion. In vitro targeting experiments showed that PLGA-targeted contrast agents with anti-HER-2 antibodies were more strongly aggregated on the surface of breast cancer cells. In vitro imaging experiments showed that the PLGA-targeted nano-ultrasound contrast imaging showed a fine and uniform point-like hyperechoic echo, and no significant attenuation of the posterior echo. This study successfully produced a PLGA-targeted nano-ultrasound contrast agent with anti-HER-2 antibody, which can specifically bind to breast cancer cells with high expression of HER-2 receptor in vitro, and the imaging effect in vitro is better.

Novel Difolate Targeting Nano-Level Ultrasound Contrast Agent for Therapy of Breast Cancer Tumor Cells

2021 ◽  
Vol 13 (7) ◽  
pp. 1295-1303
Author(s):  
Guangheng Liu ◽  
Xiangfeng Yang ◽  
Qiming Niu ◽  
Wenkui Sun
Keyword(s):  
Breast Cancer ◽  
Contrast Agent ◽  
Tumor Cells ◽  
Folate Receptor ◽  
Ultrasound Contrast Agent ◽  
Hydroxyl Group ◽  
Binding Ability ◽  
Ultrasound Contrast ◽  
Mcf 7

ABSTRACTA new type of difolate targeting nano-level ultrasound contrast agent ((folate molecule, FOL)2-TUAs) was prepared, so as to investigate its targeted binding effect with human breast cancer mammary carcinoma cells (MCF-7) in vitro. L-2-aminoadipic acid (L-2-AD) as a branch unit was inserted at the hydroxyl end of distearoyl phosphatidylethanolamine (DISP)-PEG2000-COOH to construct a tree structure. At this time, the free hydroxyl group in the distearoyl phosphatidylethanolamine (DISP)-PEG2000-COOH structure modified the FOL with the help of N-Hydroxysuccinimide/N,N'-dicyclohexylcarbodiimide (NHS/DCC). Each 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DISP-PEG2000) connected two FOLs to generate difolate targeted nanomaterials. Nano laser particle size (PS) and Zeta potential analyzer (ZPA) were applied to analyze the physical characteristics of the material such as PS and dispersion, and the enhanced development effect in vitro was detected by the ultrasonic diagnostic instrument. Besides, the targeted binding ability of the contrast agent based on this material to folate receptor (FR) overexpressing MCF-7 cells was analyzed by flow cytometry (FCM) and fluorescence microscope. In the experiment, hydrogen-1 nuclear magnetic resonance (1H NMR) demonstrated that (FOL)2-TUAs was successfully synthesized. The surface of this material was round and uniformly distributed without aggregation. According to the relative number of FOL molecules, non-targeted nano-agent (U-TUA), monofolate targeted nano-agent (FOL-TUA), and difolate targeted nano-agent ((FOL)2-TUA) were obtained. The in vitro imaging showed that different materials exhibited enhanced imaging effects in ultrasonic diagnostic equipment. FCM and fluorescence microscopy both indicated that the difolate TUA could achieve a good binding to MCF-7 cells. Most of the nano-agents were attached to the cell membrane, surrounded by red fluorophore, namely increasing the FOL content of DISP-PEG2000 chain could enhance the targeted binding ability of tumor cells.

scholarly journals FORMULATION, OPTIMIZATION AND IN VITRO EVALUATION OF 5-FLUOROURACIL LOADED LIQUORICE CRUDE PROTEIN NANOPARTICLES FOR SUSTAINED DRUG DELIVERY USING BOX-BEHNKEN DESIGN

2021 ◽  
pp. 216-226
Author(s):  
GEETHA V. S. ◽  
MALARKODI VELRAJ
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Drug Release ◽  
Crude Protein ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Box Behnken Design ◽  
Sustained Drug Delivery ◽  
Drug Loading Efficiency

Objective: To formulate, optimize and evaluate 5-fluorouracil loaded liquorice crude protein nanoparticles for sustained drug delivery using Box-Behnken design. Methods: 5-fluorouracil (5-FU) loaded liquorice crude protein (LCP) nanoparticles were prepared by desolvation method using ethanol-water (1:2 ratio), Tween-80 (2%v/v) as stabilizing agent and gluteraldehyde (8% v/v) as cross linking agent. The optimization of prepared nanoparticles was carried out using Box-Behnken design with 3 factors 2 levels and 3 responses. The independent variables were A)5-FU concentration B)LCP concentration and C) sonication time while the responses were R1) Drug entrapment efficiency R2) Drug loading efficiency and R3) Particle size. The correlation between factors and responses were studied through response surface plots and mathematical equations. The nanoparticles were evaluated for FTIR, physicochemical properties like particle size and zeta potential by Photon correlation spectroscopy (PCS) and surface morphology by TEM. The entrapment efficiency, drug loading efficiency and in vitro drug release studies in PBS pH 7.4 (24 h) were carried out. The observed values were found to be in close agreement with the predicted value obtained from the optimization process. Results: 5-fluorouracil loaded LCP nanoparticles were prepared by desolvation method, the optimization was carried out by Box-Behnken design and the final formulation was evaluated for particle size (301.1 nm), zeta-potential (-25.8mV), PDI(0.226), with entrapment efficiency (64.07%), drug loading efficiency (28.54%), in vitro drug release (65.2% in 24 h) respectively. The formulated nanoparticles show Higuchi model drug release kinetics with sustained drug delivery for 24 h in pH7.4 buffer. Conclusion: The results were proved to be the most valuable for the sustained delivery of 5-Fluorouracil using liquorice crude protein as carrier. 5-FU–LCP nanoparticles were prepared using Tween-80 as stabilizing agent and gluteraldehyde as cross-linking agent to possess ideal sustained drug release characteristics.

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