Search Results (19)

Background/Objective: The blood–brain barrier (BBB) is selectively permeable, but it also poses significant challenges for treating CNS diseases. Low-intensity focused ultrasound (LiFUS), paired with microbubbles is a promising, non-invasive technique for transiently opening the BBB, allowing enhanced drug delivery to the central nervous system (CNS). However, the downstream physiological effects following BBB opening, particularly secondary responses, are not well understood. This study aimed to characterize the time-dependent changes in BBB permeability, transporter function, and inflammatory responses in both sonicated and non-sonicated brain tissues following LiFUS treatment. Methods: We employed in situ brain perfusion to assess alterations in BBB integrity and transporter function, as well as multiplex cytokine analysis to quantify the inflammatory response. Results: Our findings show that LiFUS significantly increased vascular volume and glucose uptake, with reduced P-gp function in brain tissues six hours post treatment, indicating biphasic BBB disruption. Additionally, elevated levels of pro-inflammatory cytokines, including TNF-α and IL-6, were observed in both sonicated and non-sonicated regions. A comparative analysis between wild-type and immunodeficient mice revealed distinct patterns of cytokine release, with immunodeficient mice showing lower serum concentrations of IFN-γ and TNF-α, highlighting the potential impact of immune status on the inflammatory response to LiFUS. Conclusions: This study provides new insights into the biphasic nature of LiFUS-induced BBB disruption, emphasizing the importance of understanding the timing and extent of secondary physiological changes. Full article

This review explores a variety of techniques that utilize air injections beneath a vessel’s hull to reduce drag and consequently improve energy efficiency. It focuses on the methodologies of microbubble drag reduction (MBDR), air layer drag reduction (ALDR), and air cavity drag reduction (ACDR), offering insights into their design, operational mechanisms, and potential applications. This review provides a detailed examination of the underlying principles of these technologies, incorporating a blend of experimental research, numerical simulations, and mathematical modelling to offer a comprehensive understanding. It references recent experimental data, highlighting how these findings corroborate with numerical simulations and are further explained through mathematical models. Conclusively, this review accentuates the transformative influence of air injection methods in drag reduction within the maritime industry, emphasizing their pivotal role in boosting operational efficiency, reducing environmental impact, and driving the evolution of naval design and transportation. Through a balanced and detailed analysis, this review provides a holistic view of the current state and future prospects of these innovative resistance reduction strategies. Full article

In this work, a novel numerical method for studying the influence of gas types on drag reduction by microbubble injection is presented. Aimed at the microbubble drag reduction (MBDR) process for different types of gases, the mass transfer velocity of different types of gases in the gas–liquid phase is defined by writing a user-defined function (UDF), which reflected the influence of gas solubility on the drag reduction rate. An Eulerian multiphase flow model and the Realizable $k-\epsilon$ turbulence model are used for numerical calculation. The population balance model is used to describe the coalescence and breakup phenomena of the microbubble groups. Henry’s theorem is used to calculate the equilibrium concentration of the microbubble mixed flow. The interphase mass transfer rate of the microbubble injection process for different types of gases is studied by using permeation theory. The local mass fraction of the mixed flow is solved by the component transport equation. It is found that the larger the solubility of the gas, the lower the efficiency of MBDR. When the volume flow rate of the same type of gas is the same but the injection speed is different, the larger the solubility of the gas is, the greater the difference in the drag reduction ratio. Full article

Pulsed focused ultrasound (FUS) in combination with microbubbles has been shown to improve delivery and penetration of nanoparticles in tumors. To understand the mechanisms behind this treatment, it is important to evaluate the contribution of FUS without microbubbles on increased nanoparticle penetration and transport in the tumor extracellular matrix (ECM). A composite agarose hydrogel was made to model the porous structure, the acoustic attenuation and the hydraulic conductivity of the tumor ECM. Single-particle tracking was used as a novel method to monitor nanoparticle dynamics in the hydrogel during FUS exposure. FUS exposure at 1 MHz and 1 MPa was performed to detect any increase in nanoparticle diffusion or particle streaming at acoustic parameters relevant for FUS in combination with microbubbles. Results were compared to a model of acoustic streaming. The nanoparticles displayed anomalous diffusion in the hydrogel, and FUS with a duty cycle of 20% increased the nanoparticle diffusion coefficient by 23%. No increase in diffusion was found for lower duty cycles. FUS displaced the hydrogel itself at duty cycles above 10%; however, acoustic streaming was found to be negligible. In conclusion, pulsed FUS alone cannot explain the enhanced penetration of nanoparticles seen when using FUS and microbubbles for nanoparticle delivery, but it could be used as a tool to enhance diffusion of particles in the tumor ECM. Full article

Carbon nanocoil (CNC), a kind of quasi-one-dimensional carbon nanomaterial with a unique micro-scale helical structure, has wide application prospects in biological and environmental governance fields, due to its excellent photothermal conversion characteristics. We combine a carbon nanocoil as the laser irradiation carrier (i.e., the substance for absorbing light energy and converting light energy into heat to allow the creation of microbubbles) and a light-induced method to realize the radial short-distance transport of microbubbles. The results confirm that controlling the size of the microbubbles by laser power enables the radial transport of multiple microbubbles in a row. Light-induced CNC allows the creation of microbubbles at the start of the transport and the elimination of the microbubbles at the end of the transport, and the distance of transport between the laser irradiation site on the CNC and the location of the bubbles disappearing ranges from 10 µm to 30 µm. The circulation process of creating, transporting, and eliminating bubbles is expected to become a promising technology for soil and groundwater remediation. Full article

Fluorinated compounds have been used in clinical and biomedical applications for years. The newer class of semifluorinated alkanes (SFAs) has very interesting physicochemical properties including high gas solubility (e.g., for oxygen) and low surface tensions, such as the well-known perfluorocarbons (PFC). Due to their high propensity to assemble to interfaces, they can be used to formulate a variety of multiphase colloidal systems, including direct and reverse fluorocarbon emulsions, microbubbles and nanoemulsions, gels, dispersions, suspensions and aerosols. In addition, SFAs can dissolve lipophilic drugs and thus be used as new drug carriers or in new formulations. In vitreoretinal surgery and as eye drops, SFAs have become part of daily clinical practice. This review provides brief background information on the fluorinated compounds used in medicine and discusses the physicochemical properties and biocompatibility of SFAs. The clinically established use in vitreoretinal surgery and new developments in drug delivery as eye drops are described. The potential clinical applications for oxygen transport by SFAs as pure fluids into the lungs or as intravenous applications of SFA emulsions are presented. Finally, aspects of drug delivery with SFAs as topical, oral, intravenous (systemic) and pulmonary applications as well as protein delivery are covered. This manuscript provides an overview of the (potential) medical applications of semifluorinated alkanes. The databases of PubMed and Medline were searched until January 2023. Full article

In cases when it is desirable to transport medication through blood vessels, especially when dealing with brain cancer being confronted with the narrow arteries in the brain, the blood–brain barrier makes medical treatment difficult. There is a need of expanding the diameters of the arteries in order to facilitate the transport of medications. Recent research has pointed to various ways to improve this situation; in particular, the use an ultrasound acting on microbubbles in the blood stream has turned out to be a promising option. Here, a different possibility of enlarging the diameters of arteries is discussed, namely to exploit the electrostrictive pressure produced by internal strong, ultrashort and repetitive laser pulses. Each pulse will at first give rise to inward-directed optical forces, and once the pulse terminates, there will be a hydrodynamical bouncing flow in the outward radial direction, giving an outward impulse to the vessel wall. In the absence of friction, a symmetric oscillation picture emerges. Clearly, a supply of repetitive pulses will be needed (at a parametric resonance) to make the effect appreciable. The effect has, to our knowledge, not been discussed before. We give an approximate optical and hydrodynamical theory of it. The calculations indicate promising results for the wall pressure, although experimental work is desirable to demonstrate whether the idea can be useful in practice. Our calculation is made from a general physical perspective that is not necessarily linked to medical applications. Full article

The blood-brain barrier (BBB) controls brain homeostasis; it is formed by vascular endothelial cells that are physically connected by tight junctions (TJs). The BBB expresses efflux transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), which limit the passage of substrate molecules from blood circulation to the brain. Focused ultrasound (FUS) with microbubbles can create a local and reversible detachment of the TJs. However, very little is known about the effect of FUS on the expression of efflux transporters. We investigated the in vivo effects of moderate acoustic pressures on both P-gp and BCRP expression for up to two weeks after sonication. Magnetic resonance-guided FUS was applied in the striatum of 12 rats. P-gp and BCRP expression were determined by immunohistochemistry at 1, 3, 7, and 14 days postFUS. Our results indicate that FUS-induced BBB opening is capable of (i) decreasing P-gp expression up to 3 days after sonication in both the treated and in the contralateral brain regions and is capable of (ii) overexpressing BCRP up to 7 days after FUS in the sonicated regions only. Our findings may help improve FUS-aided drug delivery strategies by considering both the mechanical effect on the TJs and the regulation of P-gp and BCRP. Full article

Fresh produce may be contaminated by bacterial pathogens, including Listeria monocytogenes, during harvesting, packaging, or transporting. A low-intensity cavitation process with air being injected into water was studied to determine the microbubbles’ efficiency when detaching L. monocytogenes from stainless steel and the surface of fresh cucumber and avocado. Stainless steel coupons (1″ × 2″), cucumber, and avocado surfaces were inoculated with L. monocytogenes (LCDC strain). After 1, 24 or 48 h, loosely attached cells were washed off, and inoculated areas were targeted by microbubbles (~0.1–0.5 mm dia.) through a bubble diffuser (1.0 L air/min) for 1, 2, 5, or 10 min. For steel, L. monocytogenes (48 h drying) detachment peaked at 2.95 mean log reduction after 10 min of microbubbles when compared to a no-bubble treatment. After 48 h pathogen drying, cucumbers treated for 10 min showed a 1.78 mean log reduction of L. monocytogenes. For avocados, L. monocytogenes (24 h drying) detachment peaked at 1.65 log reduction after 10 min of microbubbles. Microbubble applications may be an effective, economical, and environmentally friendly way to remove L. monocytogenes, and possibly other bacterial pathogens, from food contact surfaces and the surfaces of whole, intact fresh produce. Full article

Physical activity is increasingly recognized as a strategy able to improve cancer patient outcome, and its potential to enhance treatment response is promising, despite being unclear. In our study we used a preclinical model of prostate cancer to investigate whether voluntary wheel running (VWR) could improve tumor perfusion and enhance radiotherapy (RT) efficiency. Nude athymic mice were injected with PC-3 cancer cells and either remained inactive or were housed with running wheels. Apparent microbubble transport was enhanced with VWR, which we hypothesized could improve the RT response. When repeating the experiments and adding RT, however, we observed that VWR did not influence RT efficiency. These findings contrasted with previous results and prompted us to evaluate if the lack of effects observed on tumor growth could be attributable to the physical activity modality used. Using PC-3 and PPC-1 xenografts, we randomized mice to either inactive controls, VWR, or treadmill running (TR). In both models, TR (but not VWR) slowed down tumor growth, suggesting that the anti-cancer effects of physical activity are dependent on its modalities. Providing a better understanding of which activity type should be recommended to cancer patients thus appears essential to improve treatment outcomes. Full article

In brain-targeted delivery, the transport of drugs or genes across the blood−brain barrier (BBB) is a major obstacle. Recent reports found that focused ultrasound (FUS) with microbubbles enables transient BBB opening and improvement of drug or gene delivery. We previously developed nano-sized bubbles (NBs), which were prepared based on polyethylene glycol (PEG)-modified liposomes containing echo-contrast gas, and showed that our NBs with FUS could also induce BBB opening. The aim of this study was to enhance the efficiency of delivery of pDNA into neuronal cells following transportation across the BBB using neuron-binding peptides. This study used the RVG-R9 peptide, which is a chimeric peptide synthesized by peptides derived from rabies virus glycoprotein and nonamer arginine residues. The RVG peptide is known to interact specifically with the nicotinic acetylcholine receptor in neuronal cells. To enhance the stability of the RVG-R9/pDNA complex in vivo, PEGylated polyethyleneimine (PEG-PEI) was also used. The ternary complexes composed of RVG-R9, PEG-PEI, and pDNA could interact with mouse neuroblastoma cells and deliver pDNA into the cells. Furthermore, for the in vivo experiments using NBs and FUS, gene expression was observed in the FUS-exposed brain hemispheres. These results suggest that this systemic gene delivery system could be useful for gene delivery across the BBB. Full article

If a gas volume is distributed into many microbubbles of a sub-millimetre size, the total gas/liquid surface becomes very large. This increases overall heat and/or mass transport across the sum of surfaces. The paper discusses several applications in which the use of microbubbles increases efficiency of various processes, especially in wastewater treatment and in growing microorganisms such as algae, yeast, bacteria, or primitive fungi. The problem of microbubble generation by percolation in aerator is their coalescence into larger bubbles, whatever small are the pores in the aerator in which the microbubbles are generated. The solution of this size discrepancy question was found in agitating the gas flow by a fluidic oscillator prior to its injection through the aerator. The oscillator is a no-moving-part device, simple, inexpensive, resistant to external effects like acceleration or heat, and with long maintenance-free working life. Full article

Intracellular calcium ion delivery via sonoporation has been validated to be a substitute for classical chemotherapy. However, the mechanism behind calcium sonoporation remains unclear to this day. To elucidate the role of calcium in the process of sonoporation, we aimed to investigate the influence of different calcium concentration on cell membrane permeabilization and cell viability after sonoporation. In this study, we present experimental evidence that extracellular calcium plays a major role in cell membrane molecular transport after applying ultrasound pulses. Ultrasound-microbubble cavitation in the presence of different calcium concentration affects fundamental cell bio-physio-chemical conditions: cell membrane integrity, metabolic activity, and colony formation. Corresponding vital characteristics were evaluated using three independent viability tests: propidium iodide assay (20 min–3 h), MTT assay (48 h), and cell clonogenic assay (6 d). The results indicate instant cell death, as the level of cell viability was determined to be similar within a 20 min–48 h–6 d period. Inertial cavitation activities have been determined to be directly involved in calcium delivery via sonoporation according to high correlation (R² > 0.85, p < 0.01) of inertial cavitation dose with change in either cell membrane permeabilization, metabolic activity, and colony formation efficiency. In general, calcium delivery via sonoporation induces rapid cell death, occurring within 20 min after treatment, that is the result of ultrasound mediated microbubble cavitation. Full article

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death worldwide. Poor drug delivery to tumours is thought to limit chemotherapeutic treatment efficacy. Sonoporation combines ultrasound (US) and microbubbles to increase the permeability of cell membranes. We assessed gemcitabine uptake combined with sonoporation in vitro in three PDAC cell lines (BxPC-3, MIA PaCa-2 and PANC-1). Cells were cultured in hypoxic bioreactors, while gemcitabine incubation ± sonoporation was conducted in cells with operational or inhibited nucleoside membrane transporters. Intracellular active metabolite (dFdCTP), extracellular gemcitabine, and inactive metabolite (dFdU) concentrations were measured with liquid chromatography tandem mass spectrometry. Sonoporation with increasing US intensities resulted in decreasing extracellular gemcitabine concentrations in all three cell lines with inhibited membrane transporters. In cells with inhibited membrane transporters, without sonoporation, dFdCTP concentrations were reduced down to 10% of baseline. Sonoporation partially restored gemcitabine uptake in these cells, as indicated by a moderate increase in dFdCTP concentrations (up to 37% of baseline) in MIA PaCa-2 and PANC-1. In BxPC-3, gemcitabine was effectively inactivated to dFdU, which might represent a protective mechanism against dFdCTP accumulation in these cells. Intracellular dFdCTP concentrations did not change significantly following sonoporation in any of the cell lines with operational membrane transporters, indicating that the gemcitabine activation pathway may have been saturated with the drug. Sonoporation allowed a moderate increase in gemcitabine transmembrane uptake in all three cell lines, but pre-existing nucleoside transporters were the major determinants of gemcitabine uptake and retention. Full article

Focused ultrasound (FUS) coupled with microbubbles (MB) has been found to be a promising approach to disrupt the blood-brain barrier (BBB). However, how this disruption affects drug transport remains unclear. In this study, drug transport in combination therapy of liposomes and FUS-MB-induced BBB disruption (BBBD) was investigated based on a multiphysics model. A realistic 3D brain tumour model extracted from MR images was applied. The results demonstrated the advantage of liposomes compared to free doxorubicin injection in further improving treatment when the BBB is opened under the same delivery conditions using burst sonication. This improvement was mainly due to the BBBD-enhanced transvascular transport of free doxorubicin and the sustainable supply of the drug by long-circulating liposomes. Treatment efficacy can be improved in different ways. Disrupting the BBB simultaneously with liposome bolus injection enables more free drug molecules to cross the vessel wall, while prolonging the BBBD duration could accelerate liposome transvascular transport for more effective drug release. However, the drug release rate needs to be well controlled to balance the trade-off among drug release, transvascular exchange and elimination. The results obtained in this study could provide suggestions for the future optimisation of this FUS-MB–liposome combination therapy against brain cancer. Full article