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1.
J Colloid Interface Sci ; 607(Pt 1): 836-847, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34536938

RESUMO

Perfluorocarbon emulsion droplets are hybrid colloidal materials with vast applications, ranging from imaging to drug delivery, due to their controllable phase transition into microbubbles via heat application or acoustic droplet vapourisation. The current work highlights the application of small- and ultra-small-angle neutron scattering (SANS and USANS), in combination with contrast variation techniques, in observing the in situ phase transition of polydopamine-shelled, perfluorocarbon (PDA/PFC) emulsion droplets with controlled polydispersity into microbubbles upon heating. We correlate these measurements with optical and transmission electron microscopy imaging, dynamic light scattering, and thermogravimetric analysis to characterise these emulsions, and observe their phase transition into microbubbles. Results show that the phase transition of PDA/PFC droplets with perfluorohexane (PFH), perfluoropentane (PFP), and PFH-PFP mixtures occur at temperatures that are around 30-40 °C higher than the boiling points of pure liquid PFCs, and this is influenced by the specific PFC compositions (perfluorohexane, perfluoropentane, and mixtures of these PFCs). Analysis and model fitting of neutron scattering data allowed us to monitor droplet size distributions at different temperatures, giving valuable insights into the transformation of these polydisperse, emulsion droplet systems.


Assuntos
Fluorcarbonetos , Microbolhas , Emulsões , Temperatura Alta , Indóis , Nêutrons , Polímeros
2.
Anticancer Res ; 41(10): 4761-4769, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593425

RESUMO

BACKGROUND/AIM: The early stage of atherosclerosis (AS) demonstrates a lipid-driven inflammatory cytokine increase. In the present study, we aimed to use ultrasound-targeted microbubble delivery (UTMD) therapy with the Endostar-loaded target microbubbles (MBs) to reduce AS-related inflammatory response. MATERIALS AND METHODS: Normal and lipopolysaccharide (LPS) induced human umbilical vein endothelial cells (HUVECs) were placed in a parallel-plate flow chamber. MBs were perfused through the parallel-plate flow chamber to mimic physiological blood flow. Five groups were set up: G1: Negative control (normal HUVECs); G2: LPS control (LPS induced HUVECs); G3: ICAM-1-loaded-MBs (MBi); G4: Endostar-loaded-MBs (MBe) and G5: Endostar-ICAM-1-loaded-MBs (MBei). mRNA expression of inflammatory factors and release of inflammatory cytokines were detected by RT-PCR and ELISA, respectively. RESULTS: After treatment with MBei, the mRNA expression of cell adhesion molecule-1 (CD31) (p=0.004), endothelin-1 (ET-1) (p=0.010), von willebrand factor (vWF) (p=0.018), extracellular regulated protein kinases (ERK) (p=0.046) and nuclear factor kappa B (NF-κB) (p=0.003) were significantly reduced compared to LPS-induced HUVECs. Release of inflammatory cytokines including tissue factor (TF) (p=0.033), tissue factor pathway inhibitor (TF-PI) (p=0.019), ET-1 (p=0.014), vWF (p=0.030) and blood-coagulation factor VIIα (FVIIα) (p=0.000) were also significantly reduced compared to LPS-induced HUVECs. CONCLUSION: UTMD therapy can inhibit the inflammatory response by reducing atherosclerotic-related inflammatory factors, suggesting a potential treatment at the early-stage of AS.


Assuntos
Anti-Inflamatórios/farmacologia , Fibrinolíticos/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Microbolhas , Anti-Inflamatórios/química , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , Aterosclerose/terapia , Adesão Celular , Endostatinas/química , Endostatinas/farmacologia , Fibrinolíticos/química , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/imunologia , Molécula 1 de Adesão Intercelular/metabolismo , Lipopolissacarídeos/toxicidade , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia , Ultrassom
3.
Int J Pharm ; 609: 121154, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34624449

RESUMO

Bacterial biofilms are a huge burden on our healthcare systems worldwide. The lack of specificity in diagnostic and treatment possibilities result in difficult-to-treat and persistent infections. The aim of this in vitro study was to investigate if microbubbles targeted specifically to bacteria in biofilms could be used both for diagnosis as well for sonobactericide treatment and demonstrate their theranostic potential for biofilm infection management. The antibiotic vancomycin was chemically coupled to the lipid shell of microbubbles and validated using mass spectrometry and high-axial resolution 4Pi confocal microscopy. Theranostic proof-of-principle was investigated by demonstrating the specific binding of vancomycin-decorated microbubbles (vMB) to statically and flow grown Staphylococcus aureus (S. aureus) biofilms under increasing shear stress flow conditions (0-12 dyn/cm2), as well as confirmation of microbubble oscillation and biofilm disruption upon ultrasound exposure (2 MHz, 250 kPa, and 5,000 or 10,000 cycles) during flow shear stress of 5 dyn/cm2 using time-lapse confocal microscopy combined with the Brandaris 128 ultra-high-speed camera. Vancomycin was successfully incorporated into the microbubble lipid shell. vMB bound significantly more often than control microbubbles to biofilms, also in the presence of free vancomycin (up to 1000 µg/mL) and remained bound under increasing shear stress flow conditions (up to 12 dyn/cm2). Upon ultrasound insonification biofilm area was reduced of up to 28%, as confirmed by confocal microscopy. Our results confirm the successful production of vMB and support their potential as a new theranostic tool for S. aureus biofilm infections by allowing for specific bacterial detection and biofilm disruption.


Assuntos
Staphylococcus aureus , Vancomicina , Antibacterianos , Biofilmes , Testes de Sensibilidade Microbiana , Microbolhas , Medicina de Precisão
4.
J Acoust Soc Am ; 150(3): 1750, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34598597

RESUMO

Perfluoropentane droplets with cellulose nanofibers (CNF) shells have demonstrated better stability and easier surface modification as ultrasound contrast agents and drug delivery vehicles. This paper presents a theoretical model assuming a four-phase state "inverse antibubble," with the core filled with gas perfluoropentane surrounded by liquid perfluoropentane. A continuous, incompressible, and viscoelastic stabilizing layer separates the core from the surrounding water. A parametric study is performed to predict the frequency-dependent attenuation coefficient, the speed of sound, and the resonance frequency of the droplets which have a mean diameter of 2.47 ± 0.95 µm. Results reveal that the CNF-stabilized perfluoropentane droplets can be modeled in a Rayleigh-Plesset like equation. We conclude that the shell strongly influences the acoustic behavior of the droplets and the resonance frequency largely depends on the initial gas cavity radius. More specifically, the peak attenuation coefficient and peak-to-peak speed of sound decrease with increasing shear modulus, shear viscosity, and shell thickness, while they increase with increasing gas cavity radius and concentration. The resonance frequency increases as shear modulus and shell thickness increase, while it decreases as shear viscosity and gas cavity radius increase. It is worth mentioning that droplet concentration has no effect on the resonance frequency.


Assuntos
Microbolhas , Nanofibras , Acústica , Celulose , Fluorcarbonetos
5.
J Acoust Soc Am ; 150(2): 1577, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34470259

RESUMO

Surfactant-coated gas microbubbles are widely used as contrast agents in ultrasound imaging and increasingly in therapeutic applications. The response of microbubbles to ultrasound can be strongly influenced by their size and coating properties, and hence the production method. Ultrasonic emulsification (sonication) is the most commonly employed method and can generate high concentrations of microbubbles rapidly, but with a broad size distribution, and there is a risk of contamination and/or degradation of sensitive components. Microfluidic devices provide excellent control over microbubble size, but are often challenging or costly to manufacture, offer low production rates (<106s-1), and are prone to clogging. In this study, a hybrid sonication-microfluidic or "sonofluidic" device was developed. Bubbles of ∼180 µm diameter were produced rapidly in a T-junction and subsequently exposed to ultrasound (71-73 kHz) within a microchannel, generating microbubbles (mean diameter: 1-2 µm) at a rate of >108s-1 using a single device. Microbubbles were prepared using either the sonofluidic device or conventional sonication, and their size, concentration, and stability were comparable. The mean diameter, concentration, and stability were found to be comparable between techniques, but the microbubbles produced by the sonofluidic device were all <5 µm in diameter and thus did not require any post-production fractionation.


Assuntos
Dispositivos Lab-On-A-Chip , Microbolhas , Meios de Contraste , Microfluídica , Ultrassonografia
6.
BMC Cancer ; 21(1): 991, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479484

RESUMO

BACKGROUND: The study here investigated quantitative ultrasound (QUS) parameters to assess tumour response to ultrasound-stimulated microbubbles (USMB) and hyperthermia (HT) treatment in vivo. Mice bearing prostate cancer xenografts were exposed to various treatment conditions including 1% (v/v) Definity microbubbles stimulated at ultrasound pressures 246 kPa and 570 kPa and HT duration of 0, 10, 40, and 50 min. Ultrasound radiofrequency (RF) data were collected using an ultrasound transducer with a central frequency of 25 MHz. QUS parameters based on form factor models were used as potential biomarkers of cell death in prostate cancer xenografts. RESULTS: The average acoustic concentration (AAC) parameter from spherical gaussian and the fluid-filled spherical models were the most efficient imaging biomarker of cell death. Statistical significant increases of AAC were found in the combined treatment groups: 246 kPa + 40 min, 246 kPa + 50 min, and 570 kPa + 50 min, in comparison with control tumours (0 kPa + 0 min). Changes in AAC correlates strongly (r2 = 0.62) with cell death fraction quantified from the histopathological analysis. CONCLUSION: Scattering property estimates from spherical gaussian and fluid-filled spherical models are useful imaging biomarkers for assessing tumour response to treatment. Our observation of changes in AAC from high ultrasound frequencies was consistent with previous findings where parameters related to the backscatter intensity (AAC) increased with cell death.


Assuntos
Hipertermia Induzida/métodos , Neoplasias da Próstata/terapia , Ultrassom/métodos , Animais , Apoptose , Proliferação de Células , Terapia Combinada , Humanos , Masculino , Camundongos , Camundongos SCID , Microbolhas , Neoplasias da Próstata/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
7.
J Vis Exp ; (175)2021 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-34542531

RESUMO

Targeting of microbubbles (ultrasound contrast agents for molecular imaging) has been researched for more than two decades. However, methods of microbubble preparation and targeting ligand attachment are cumbersome, complicated, and lengthy. Therefore, there is a need to simplify the targeted microbubble preparation procedure to bring it closer to clinical translation. The purpose of this publication is to provide a detailed description and explanation of the steps necessary for targeted microbubble preparation, functional characterization and testing. A sequence of the optimized and simplified procedures is presented for two systems: a biotin-streptavidin targeting pair model, and a cyclic RGD peptide targeting the recombinant αvß3 protein, which is overexpressed on the endothelial lining of the tumor neovasculature. Here, we show the following: covalent coupling of the targeting ligand to a lipid anchor, assessment of the reagent quality, and tests that confirm the successful completion of the reaction; preparation of the aqueous precursor medium containing microbubble shell components, followed by microbubble preparation via amalgamation; assessment of the efficacy of lipid transfer onto the microbubble stabilizer shell; adjustment of microbubble size distribution by flotation at normal gravity to remove larger microbubbles that might be detrimental for in vivo use; assessment of microbubble size distribution by electrozone sensing; evaluation of targeted binding of the microbubbles to receptor-coated surface in a static binding assay test (in an inverted dish); and evaluation of targeted binding of the microbubbles to receptor-coated surface in a parallel plate flow chamber test.


Assuntos
Meios de Contraste , Microbolhas , Imagem Molecular , Estreptavidina , Ultrassonografia
8.
J Control Release ; 338: 731-741, 2021 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-34530050

RESUMO

Drug-loaded nanoscale cavitation agents, called nanodroplets, are an attractive solution to enhance and localize drug delivery, offering increased stability and prolonged half-life in circulation compared to microbubbles. However, the spatial precision with which drug can be released and delivered into brain tissue from such agents has not been directly mapped. Decafluorobutane lipid-shell droplets (206 +/- 6 nm) were loaded with a fluorescent blood-brain barrier (BBB)-penetrating dye (Nile Blue) and vaporized with ultrasound (1.66 MHz, 10 ms pulse length, 1 Hz pulse repetition frequency), generating transient echogenic microbubbles and delivering the encapsulated dye. The distribution and intensity of released fluorophore was mapped in a tissue-mimicking phantom, and in the brain of rats (Sprague Dawley, N = 4, n = 16). The release and distribution of dye was found to be pressure-dependent (0.2-3.5 MPa) and to occur only above the vaporization threshold of the nanodroplets (1.5 +/- 0.25 MPa in vitro, 2.4 +/- 0.05 MPa in vivo). Dye delivery was achieved with sub-millimetre spatial precision, covering an area of 0.4 to 1.5 mm in diameter, determined by the sonication pressure. The distribution and intensity of dye released at depth in the brain followed the axial pressure profile of the ultrasound beam. Nile Blue (354 Da, LogP 2.7) was compared to Nile Red (318 Da, LogP 3.8) and Quantum Dots (CdSe/ZnS, 5 nm diameter) to visualize the role of molecule size and lipophilicity in crossing the intact BBB following triggered release. Acoustic emissions were shown to predict the successful delivery of the BBB-penetrating dye and the extent of the distribution, demonstrating the theranostic capabilities of nanoscale droplets to precisely localize drug delivery in the brain.


Assuntos
Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Animais , Barreira Hematoencefálica , Encéfalo/diagnóstico por imagem , Microbolhas , Ratos , Ratos Sprague-Dawley , Sonicação
9.
Med Phys ; 48(11): 6765-6780, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34580883

RESUMO

PURPOSE: An antibubble is an encapsulated gas bubble with an incompressible inclusion inside the gas phase. Current-generation ultrasound contrast agents are bubble-based: they contain encapsulated gas bubbles with no inclusions. The objective of this work is to determine the linear and nonlinear responses of an antibubble contrast agent in comparison to two bubble-based ultrasound contrast agents, that is, reference bubbles and SonoVue TM . METHODS: Side scatter and attenuation of the three contrast agents were measured, using single-element ultrasound transducers, operating at 1.0, 2.25, and 3.5 MHz. The scatter measurements were performed at acoustic pressures of 200 and 300 kPa for 1.0 MHz, 300 kPa, and 450 kPa for 2.25 MHz, and 370 and 560 kPa for 3.5 MHz. Attenuation measurements were conducted at pressures of 13, 55, and 50 kPa for 1.0, 2.25, and 3.5 MHz, respectively. In addition, a dynamic contrast-enhanced ultrasound measurement was performed, imaging the contrast agent flow through a vascular phantom with a commercial diagnostic linear array probe. RESULTS: Antibubbles generated equivalent or stronger harmonic signal, compared to bubble-based ultrasound contrast agents. The second harmonic side-scatter amplitude of the antibubble agent was up to 3 dB greater than that of reference bubble agent and up to 4 dB greater than that of SonoVue TM at the estimated concentration of 8 × 10 4 bubbles/mL. For ultrasound with a center transmit frequency of 1.0 MHz, the attenuation coefficient of the antibubble agent was 8.7 dB/cm, whereas the attenuation coefficient of the reference agent was 7.7 and 0.3 dB/cm for SonoVue TM . At 2.25 MHz, the attenuation coefficients were 9.7, 3.0, and 0.6 dB/cm, respectively. For 3.5 MHz, they were 4.4, 1.8, and 1.0 dB/cm, respectively. A dynamic contrast-enhanced ultrasound recording showed the nonlinear signal of the antibubble agent to be 31% greater than for reference bubbles and 23% lower than SonoVue TM at a high concentration of 2 × 10 6 bubbles/mL. CONCLUSION: Endoskeletal antibubbles generate comparable or greater higher harmonics than reference bubbles and SonoVue TM . As a result, antibubbles with liquid therapeutic agents inside the gas phase have high potential to become a traceable therapeutic agent.


Assuntos
Acústica , Meios de Contraste , Microbolhas , Imagens de Fantasmas , Fenômenos Físicos , Ultrassonografia
10.
J Control Release ; 338: 358-366, 2021 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-34481018

RESUMO

FOLFIRINOX and FOLFOXIRI are combination chemotherapy treatments that incorporate the same drug cocktail (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) but exploit an altered dosing regimen when used in the management of pancreatic and colorectal cancer, respectively. Both have proven effective in extending life when used to treat patients with metastatic disease but are accompanied by significant adverse effects. To facilitate improved tumour-targeting of this drug combination, an ultrasound responsive microbubble formulation loaded with 5-fluorouridine, irinotecan and oxaliplatin (FIRINOX MB) was developed and its efficacy tested, together with the non-toxic folinic acid, in preclinical murine models of pancreatic and colorectal cancer. A significant improvement in tumour growth delay was observed in both models following ultrasound targeted microbubble destruction (UTMD) mediated FIRINOX treatment with pancreatic tumours 189% and colorectal tumours 82% smaller at the conclusion of the study when compared to animals treated with a standard dose of FOLFIRINOX. Survival prospects were also improved for animals in the UTMD mediated FIRINOX treatment group with an average survival of 22.17 ± 12.19 days (pancreatic) and 44.40 ± 3.85 days (colorectal) compared to standard FOLFIRINOX treatment (15.83 ± 4.17 days(pancreatic) and 37.50 ± 7.72 days (colon)). Notably, this improved efficacy was achieved using FIRINOX MB that contained 5-fluorouricil, irinotecan and oxaliplatin loadings that were 13.44-fold, 9.19-fold and 1.53-fold lower than used for the standard FOLFIRINOX treatment. These results suggest that UTMD enhances delivery of FIRINOX chemotherapy, making it significantly more effective at a substantially lower dose. In addition, the reduced systemic levels of 5-fluorouracil, irinotecan and oxaliplatin should also make the treatment more tolerable and reduce the adverse effects often associated with this treatment.


Assuntos
Neoplasias do Colo , Neoplasias Pancreáticas , Animais , Protocolos de Quimioterapia Combinada Antineoplásica , Camptotecina/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/uso terapêutico , Humanos , Irinotecano , Leucovorina/uso terapêutico , Camundongos , Microbolhas , Oxaliplatina , Neoplasias Pancreáticas/tratamento farmacológico , Resultado do Tratamento , Uridina/análogos & derivados
11.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(8): 1220-1225, 2021 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-34549714

RESUMO

OBJECTIVE: To investigate the effect of DR5-mediated docetaxel-targeted lipid microbubbles (MBs) combined with ultrasound-targeted microbubble destruction on apoptosis and expressions of Bcl-2, nuclear factor-κB(NF-κB), caspase-8, and DR5 in human HepG2 cells. METHODS: HepG2 cells were treated with docetaxel at its 50% inhibitory concentration (IC50) of 5 nmol/L, docetaxel combined with ultrasound, blank MBs, blank MBs combined with ultrasound (0.5 W/cm2 for 45 s), drugloaded lipid MBs (DLLM), DLLM combined with ultrasound, DR5-mediated DLLM (DR5-DLLM), or DR5-DLLM combined with ultrasound.After the treatments, the cells were further cultured for 24 h, and CCK-8 assay, TUNEL staining and flow cytometry were used to assess cell proliferation, apoptosis, and cell cycle changes; the changes in mRNA and protein expression levels of Bcl-2, NF-κB, caspase-8, and DR5 were detected with RT-qPCR and Western blotting. RESULTS: Among all the treatments, DR5-DLLM combined with ultrasound produced the strongest effects to inhibit the proliferation (P < 0.001), promote apoptosis (P < 0.001), and cause G2/M cell cycle arrest (P < 0.001) in HepG2 cells.The combined treatment with DR5-DLLM and ultrasound also significantly downregulated Bcl-2 and NF-κB (P < 0.001) and upregulated DR5 and caspase-8 expressions (P < 0.001) at both the mRNA and protein levels. CONCLUSION: DR5-DLLM combined with ultrasound-targeted microbubble destruction can induce G2/M cell cycle arrest, proliferation inhibition and apoptosis in HepG2 cells by downregulating Bcl-2 and NF-κB and upregulating DR5 and caspase-8 expressions, indicating its value as a novel ultrasoundtargeted therapy for liver cancer.


Assuntos
Apoptose , Microbolhas , Proliferação de Células , Docetaxel/farmacologia , Células Hep G2 , Humanos , Lipídeos
12.
Int J Nanomedicine ; 16: 6265-6280, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539179

RESUMO

Objective: To prepare a new type of dual-target microbubble loaded with anti-miR-33 (ANM33). Methods: Carrier core nanobubbles (NBs) were prepared by thin film hydration, and microbubbles loaded with PM1 (PCNBs) were prepared by grafting DSPE-PEG2000-maleimide-PM1 onto the NB surface. ANM33 was connected via electrostatic adsorption and covalent bonding, and hyaluronic acid (HA) was covalently connected. PM1 and HA were the targets, and ANM33 was the intervention drug. To evaluate the general physical and chemical properties of the prepared dual-target microbubbles loaded with ANM33 (HA-PANBs), we observed their morphology, particle size and surface potential while monitoring their stability and in vitro imaging ability, evaluated their toxic effect on cells and verified their ability to target cells. Results: HA-PANBs had a regular morphology and good stability. The average particle size measured by a Malvern potentiometer was 1421.75±163.23 nm, and the average surface potential was -5.51±1.87 mV. PM1 and ANM33 were effectively connected to the NBs. The PM1, ANM33, and HA binding reached 89.0±1.1%, 65.02±5.0%, and 61.4±3.5%, respectively, and the maximum binding reached 2 µg, 5 µg, and 7 µg/108 microbubbles, respectively. HA-PANBs had no obvious toxic effects on cells, and their ability to continuously enhance imaging in vitro persisted for more than 15 minutes, obviously targeting foam cells in the early stage of AS. Conclusion: HA-PANBs are ideal ultrasound contrast agents. The successful, firm connection of PM1 and HA to the NBs significantly increased the amount of carried ANM33. When microbubbles prepared with 2:4:7 PM1:ANM33:HA were used as a contrast agent, they had a high ANM33 carrying capacity, stable physical properties, and significantly enhanced imaging and targeting of foam cells in the early stage of AS.


Assuntos
Meios de Contraste , Microbolhas , Antagomirs , Tamanho da Partícula , Ultrassonografia
13.
J Acoust Soc Am ; 150(1): 241, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34340483

RESUMO

Double-strand breaks (DSBs) of giant DNA molecules after exposure to 1.0 MHz pulsed-wave ultrasound were quantitatively evaluated by single-molecule observation of giant DNA (T4 GT7 DNA; 166 kbp) through fluorescence microscopy. Aqueous solutions of DNA were exposed to ultrasonic waves with different sound pressures, repetition periods (1, 2, 5 ms), and pulse durations (5, 10, 50 µs). Below a threshold value of sound pressure, almost no double-strand breaks were generated, and above the threshold, the degree of damage increased in an accelerated manner as the pressure increased. DNA damage was much more severe for exposure to ultrasound with a shorter pulse duration. In addition, a longer pulse repetition period caused worse damage in DNA molecules. The effect of microbubbles on the damage induced by exposure to ultrasound had also been studied. While a result showed that a very small amount of microbubbles increased DSBs of DNA, this effect of microbubbles only weakly depended on their concentrations.


Assuntos
DNA , Ondas Ultrassônicas , Microbolhas , Ultrassonografia
14.
Curr Cardiol Rep ; 23(10): 133, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34410529

RESUMO

PURPOSE OF REVIEW: High mechanical index impulses from a diagnostic transducer are utilized in myocardial perfusion imaging, but can also be utilized therapeutically in three cardiovascular applications: (a) thrombus dissolution (sonothrombolysis), (b) improving microvascular flow in ischemic territories (sonoperfusion), and (c) targeted drug and nucleic acid delivery. The targeted therapeutic effect appears to be based on acoustic cavitation of the intravascular microbubbles which results in endothelial shear and pore formation, as well as mechanical destruction of thrombi. RECENT FINDINGS: Within the last 5 years, clinical trials have been performed in acute myocardial infarction demonstrating successful reductions in myocardial infarct size with sonothrombolysis added to current guideline-based treatment. In patients with severe peripheral arterial disease, brief improvements in calf microvascular blood flow have been observed for 1 h after 10 min of sonoperfusion therapy. Targeted ultrasound therapies are developing for prevention of microvascular obstruction in acute coronary syndromes and peripheral vascular disease.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Terapia por Ultrassom , Humanos , Microbolhas , Infarto do Miocárdio/terapia , Ultrassonografia
15.
J Biomed Nanotechnol ; 17(7): 1293-1304, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446133

RESUMO

De novo designed lipidated methotrexate was synthesized and self-assembled into microbubbles for targeted rheumatoid arthritis theranostic treatment. Controlled lipidatedmethotrexate delivery was achieved by ultrasound-targetedmicrobubble destruction technique. Methotrexate was dissociated inflammatory microenvironment of synovial cavity, owing to representive low pH and enriched leucocyte esterase. We first manipulated methotrexate controlled release with RAW 264.7 cell line in vitro and further verified with rheumatoid arthritis rabbits in vivo. Results showed that lipidated methotrexate microbubbles precisely affected infection focus and significantly enhanced rheumatoid arthritis curative effect comparing with dissociative methotrexate. This study indicates that lipidated methotrexate microbubbles might be considered as a promising rheumatoid arthritis theranostics medicine.


Assuntos
Antirreumáticos , Artrite Reumatoide , Animais , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Metotrexato , Microbolhas , Medicina de Precisão , Coelhos , Ultrassom
16.
Phys Med ; 89: 232-242, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34425514

RESUMO

PURPOSE: We investigate the vaporization of phase-change ultrasound contrast agents using photon radiation for dosimetry perspectives in radiotherapy. METHODS: We studied superheated perfluorobutane nanodroplets with a crosslinked poly(vinylalcohol) shell. The nanodroplets' physico-chemical properties, and their acoustic transition have been assessed firstly. Then, poly(vinylalcohol)-perfluorobutane nanodroplets were dispersed in poly(acrylamide) hydrogel phantoms and exposed to a photon beam. We addressed the effect of several parameters influencing the nanodroplets radiation sensitivity (energy/delivered dose/dose rate/temperature). The nanodroplets-vaporization post-photon exposure was evaluated using ultrasound imaging at a low mechanical index. RESULTS: Poly(vinylalcohol)-perfluorobutane nanodroplets show a good colloidal stability over four weeks and remain highly stable at temperatures up to 78 °C. Nanodroplets acoustically-triggered phase transition leads to microbubbles with diameters <10 µm and an activation threshold of mechanical index = 0.4, at 7.5 MHz. A small number of vaporization events occur post-photon exposure (6MV/15MV), at doses between 2 and 10 Gy, leading to ultrasound contrast increase up to 60% at RT. The nanodroplets become efficiently sensitive to photons when heated to a temperature of 65 °C (while remaining below the superheat limit temperature) during irradiation. CONCLUSIONS: Nanodroplets' core is linked to the degree of superheat in the metastable state and plays a critical role in determining nanodroplet' stability and sensitivity to ionizing radiation, requiring higher or lower linear energy transfer vaporization thresholds. While poly(vinylalcohol)-perfluorobutane nanodroplets could be slightly activated by photons at ambient conditions, a good balance between the degree of superheat and stability will aim at optimizing the design of nanodroplets to reach high sensitivity to photons at physiological conditions.


Assuntos
Nanopartículas , Fótons , Meios de Contraste , Microbolhas , Ultrassonografia , Volatilização
17.
Sci Total Environ ; 798: 149289, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34340085

RESUMO

Reverse osmosis (RO) is being used in many water reclamation facilities to produce high quality water that can be reused for different purposes. As a part of the RO process, a reject stream is produced as the reverse osmosis concentrate (ROC), which contains elevated levels of contaminants compared to the source water. Effective treatment and safe disposal of ROC via cost-effective means is very challenging. This study aims to develop a robust microbubble ozonation-biological process for industrial ROC treatment with a target effluent chemical oxygen demand (COD) lower than 60 mg/L. As compared to macrobubble ozonation, microbubble ozonation exhibited better ozone dissolution and 29% higher COD removal efficiency with the same ozone dosage. Under the optimum operating conditions with ozone dosage of 30 mg/L, ROC natural pH of 8.67 and ozonation duration of 1 h, microbubble ozonation achieved 42% COD removal efficiency while increasing the BOD5/COD ratio (ratio of biological oxygen demand over 5 days to the corresponding chemical oxygen demand) in ROC from 0.042 to 0.216. A biological activated carbon (BAC) column with an empty bed contact time (EBCT) of 120 min was combined with microbubble ozonation for continuous ROC treatment. Over the 100-day operation, the combined system performed consistent organics removal with an average effluent COD of 45 mg/L. Both LC-OCD data and fluorescence EEM spectra confirmed humic substances were the dominant organic species in ROC. Ozone pre-treatment could achieve significant removal of humic substances in raw ROC. ATP analysis found that ozone pre-treatment enhanced BAC biofilm activity by around 5 folds. 5 min acute toxicity assessment with Aliivibrio fischeri showed 4 times reduction of bioluminescence inhibition in ozone treated ROC. From the environmental point of view, Life cycle assessment (LCA) results demonstrated that Ozone-BAC system had significant environmental burdens on climate change and human toxicity due to the electricity production process. These environmental impacts can be mitigated by optimizing the ozonation process with reduced ozone dosage or utilizing renewable energy sources for electricity generation.


Assuntos
Ozônio , Poluentes Químicos da Água , Carvão Vegetal , Meio Ambiente , Humanos , Microbolhas , Osmose , Poluentes Químicos da Água/análise
18.
J Vis Exp ; (173)2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34338676

RESUMO

Microbubbles are the most commonly used imaging contrast agent in ultrasound. However, due to their size, they are limited to vascular compartments. These microbubbles can be condensed or formulated as perfluorocarbon nanodroplets (PFCnDs) that are small enough to extravasate and then be triggered acoustically at the target site. These nanoparticles can be further enhanced by including an optical absorber such as near infrared organic dye or nanoparticles (e.g., copper sulfide nanoparticles or gold nanoparticles/nanorods). Optically tagged PFCnDs can be vaporized through laser irradiation in a process known as optical droplet vaporization (ODV). This process of activation enables the use of high boiling point perfluorocarbon cores, which cannot be vaporized acoustically under the maximum mechanical index threshold for diagnostic imaging. Higher boiling point cores result in droplets that will recondense after vaporization, resulting in "blinking" PFCnDs that briefly produce contrast after vaporization before condensing back into nanodroplet form. This process can be repeated to produce contrast on demand, allowing for the background free imaging, multiplexing, super-resolution, and contrast enhancement through both optical and acoustic modulation. This article will demonstrate how to synthesize optically-triggerable, lipid shell PFCnDs utilizing probe sonication, create polyacrylamide phantoms to characterize the nanodroplets, and acoustically modulate the PFCnDs after ODV to improve contrast.


Assuntos
Fluorcarbonetos , Nanopartículas Metálicas , Nanopartículas , Acústica , Meios de Contraste , Ouro , Microbolhas
19.
Colloids Surf B Biointerfaces ; 208: 112049, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34454362

RESUMO

We have developed oxygen filled microbubbles, SE61O2, for localized, ultrasound-triggered oxygen delivery to hypoxic tumors prior to radiation therapy. Microbubbles, created by sonication, have a shell composed of D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and sorbitan monostearate. Preliminary studies in mice with breast tumor xenographs showed that increases in oxygen partial pressure levels lasted less than 3 min, which is insufficient for most clinical applications. Hence, we investigated the potential of incorporating a hydrophobic antiglycolytic drug, modeled with Nile red. A new fabrication method was developed by first creating drug-loaded TPGS micelles. The resulting microbubbles had similar shell compositions, physical size, morphology, and acoustic properties as the original method. However, microbubble yield was more than doubled, resulting in twice the encapsulation efficiency. For the TPGS micelle method these include similar shell compositions (94.4 ± 0.6 % Montane 60), physical size post freeze-drying and reconstitution (1.57 ± 0.42 µm), morphology (spherical), and acoustic properties (maximum enhancement 19.92 ± 0.55 dB). However, microbubble yield was more than doubled, resulting in twice the encapsulation efficiency (up to 10.49 %). We propose that a nonideal mixture is formed when the surfactants are combined by the standard method, resulting in the formation of mixed micelles that are more stable, making microbubble creation more difficult during the sonication step.


Assuntos
Microbolhas , Tensoativos , Animais , Portadores de Fármacos , Camundongos , Micelas , Oxigênio , Polietilenoglicóis
20.
Molecules ; 26(12)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199327

RESUMO

The application of insulin-like growth factor 1 (IGF-1) to the round window membrane (RWM) is an emerging treatment for inner ear diseases. RWM permeability is the key factor for efficient IGF-1 delivery. Ultrasound microbubbles (USMBs) can increase drug permeation through the RWM. In the present study, the enhancing effect of USMBs on the efficacy of IGF-1 application and the treatment effect of USMB-mediated IGF-1 delivery for noise-induced hearing loss (NIHL) were investigated. Forty-seven guinea pigs were assigned to three groups: the USM group, which received local application of recombinant human IGF-1 (rhIGF-1, 10 µg/µL) following application of USMBs to the RWM; the RWS group, which received IGF-1 application alone; and the saline-treated group. The perilymphatic concentration of rhIGF-1 in the USM group was 1.95- and 1.67- fold of that in the RWS group, 2 and 24 h after treatment, respectively. After 5 h of 118 dB SPL noise exposure, the USM group had the lowest threshold shift in auditory brainstem response, least loss of cochlear outer hair cells, and least reduction in the number of synaptic ribbons on postexposure day 28 among the three groups. The combination of USMB and IGF-1 led to a better therapeutic response to NIHL. Two hours after treatment, the USM group had significantly higher levels of Akt1 and Mapk3 gene expression than the other two groups. The most intense immunostaining for phosphor-AKT and phospho-ERK1/2 was detected in the cochlea in the USM group. These results suggested that USMB can be applied to enhance the efficacy of IGF-1 therapy in the treatment of inner ear diseases.


Assuntos
Cóclea/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Perda Auditiva Provocada por Ruído/tratamento farmacológico , Fator de Crescimento Insulin-Like I/farmacologia , Microbolhas/uso terapêutico , Janela da Cóclea/efeitos dos fármacos , Ondas Ultrassônicas , Animais , Cóclea/metabolismo , Modelos Animais de Doenças , Cobaias , Perda Auditiva Provocada por Ruído/metabolismo , Perda Auditiva Provocada por Ruído/patologia , Janela da Cóclea/metabolismo
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