Ultrasound-triggered nicotine release from nicotine-loaded cellulose hydrogel

Ultrasound (US)-triggered nicotine release system in a cellulose hydrogel drug carrier was developed with three different cellulose concentrations of 0.45 wt%, 0.9 wt%, and 1.8 wt%. The nicotine-loaded cellulose hydrogels were fabricated by the phase inversion method when the nicotine and cellulose mixture in the 6 wt% LiCl/N, N-dimethylacetamide solvent was exposed to water vapor at room temperature. Nicotine was used as the medicine due to its revealed therapeutic potential for neurodegenerative diseases like Alzheimer's and Parkinson's diseases. The behavior of US-triggered nicotine release from nicotine-cellulose hydrogel was studied at 43 kHz US frequency at the changing US output powers of 0 W, 5 W, 10 W, 20 W, 30 W, and 40 W. The significant US-triggered nicotine release enhancement was noted for the hydrogels made with 0.9 wt% and 1.8 wt% cellulose loading. The matrix made with 0.9 wt% cellulose was exhibited the highest nicotine release at the 40 W US power, and differences in nicotine release at different US powers were noticeable than at 0.45 wt% and 1.8 wt% cellulose loadings. For the three cellulose hydrogel systems, the storage modulus (G′) values at the 0.01 wt% strain rate were dropped from their initial values due to the US irradiation. This reduction was proportionately decreased when the US power was increased. The deconvolution of FTIR spectra of nicotine-loaded cellulose films before and after US exposure was suggested breakage of cellulose-nicotine and cellulose-water in the matrix; thus, the stimulated nicotine release from the cellulose matrix was promoted by the US irradiation.     

Systematic characterization of drug release profiles from finite-sized hydrogels

Diffusion is often used as the primary method of molecular transport in drug delivery schemes. We present a systematic investigation of the Weibull and Peppas functions as useful tools in quantifying drug release profiles. The data is obtained from 2D simulated hydrogels and diffusion is modeled using an exact enumeration scheme. We show the fitting parameters to be largely time-dependent and therefore unreliable in indicating fundamental characteristics of the underlying physical mechanism. The parameters in the Weibull function however, have a stable regime when characterizing release profiles; we propose a simple iterative test that can be used to ensure that one is in this stable regime. Also, the mechanism of diffusion is shown to be independent of obstacle density in hydrogels that are larger than their respective characteristic lengths; a homogeneous obstacle distribution can therefore be replaced by an effective viscosity.     

Ultrasound response of viscoelastic changes of cellulose hydrogels triggered with Sono-deviced rheometer

Sono-deviced rheometer,which enabled viscoelastic properties under ultrasound operation, was used to investigate for cellulosic hydrogels. The viscoelastic behavior was compared in cellulosic hydrogels prepared at 0.5, 1 and 2 wt% concentration in the DMAc/LiCl solution. The sono-deviced equipment could measure the effect of changes in storage modulus G’ and loss modulus G” under 43 kHz ultrasound exposure. It was noted that the 43 kHz ultrasound significantly changed the values of the G′, meaning that the hydrogel was soften under the exposure within few seconds. When the ultrasound exposed 50 W of the out-put power at 1% strain, the G′ value of 4.2x10⁴ Pa was reduced to 4.0x10³ Pa during 5 min of the US interval. The declined lowering value of G’ then returned to the original moduli value when ultrasound was stopped. The values of both G’ and G” values were measured at applied strain % during viscoelastic measurements of the cellulosic hydrogels without and with ultrasound exposure. The comparison indicated that the ultrasound has reinforced the effect of the mechanical deformation of the hydrogel structure at the smaller mechanical strain values applied during the ultrasound operation. The ultrasound soften effect on the viscoelastic change efficiently occurred in the 0.5 wt% sample and easily induced the structural deformation probably due to the breakage of hydrogen bonds in the cellulose hydrogels.     

A single step ultrasound-assisted nitrocellulose synthesis from microcrystalline cellulose

Nitrocellulose is a nitrated cellulose polymer with a broad application in industry. Depending on the nitrogen content, this polymer can be used for manufacturing explosives, varnishes, clothes, and films, being considered a product of high value-added. In this work, the use of ultrasound was investigated for the intensification of nitrocellulose synthesis from microcrystalline cellulose. The ultrasound-assisted nitrocellulose synthesis (UANS) was carried out using several ultrasound systems, such as baths and cup horns, allowing the evaluation of the frequency (from 20 to 130 kHz) and delivered power (from 23 to 134 W dm⁻³) to the reaction medium. The following parameters were evaluated: acid mixture (H₂SO₄, H₃PO₄, CH₂O₂ or CH₃COOH with HNO₃, 2 to 14.4 mol L⁻¹), ultrasound amplitude (10 to 70%) and reaction time (5 to 50 min). Better nitrocellulose yield (nitrogen content of 12.5% was obtained from 1 g of microcrystalline cellulose employing a cup horn system operating at 20 kHz, 750 W of nominal power with 60% of amplitude, 25 mL of acid solution (13.6 mL of 18.4 mol L⁻¹ H₂SO₄ + 9.2 mL of 14.4 mol L⁻¹ HNO₃ + 2.2 mL H₂O), at 30 °C for 30 min. At silent conditions (mechanical stirring ranging from 100 to 500 rpm), the nitrogen content was lower than 11.8% which demonstrate the ultrasound effects for nitrocellulose synthesis.     

Ultrasound responsive carbon monoxide releasing micelle

Carbon monoxide (CO), an endogenously produced gasotransmitter, has shown various therapeutic effects in previous studies. In this work, we developed an ultrasound responsive micelle for localized CO delivery. The micelle is composed of a pluronic shell and a core of a CO releasing molecule, CORM-2. The mechanism is based on the ultrasound response of pluronics, and the reaction between CORM-2 and certain biomolecules, e.g. cysteine. The latter allows CO release without significantly breaking the micelles. In a 3.5 mM cysteine solution, the micelles released low level of CO, indicating effective encapsulation of CORM-2. Treatment with a low intensity, non-focused ultrasound led to four times as much CO as the sample without ultrasonication, which is close to that of unencapsulated CORM-2. Significantly reduced proliferation of prostate cancer cells (PC-3) was observed 24 h after the PC-3 cells were treated with the CORM-2 micelles followed by ultrasound activation.     

Synthesis of cellulose nanocrystals (CNCs) from cotton using ultrasound-assisted acid hydrolysis

This present work reports the synthesis of Cellulose nanocrystals (CNCs) from cotton using an ultrasound-assisted acid hydrolysis. Further, the synthesized CNCs was comprehensively characterized using Fourier Transform Infrared Spectroscopy (FTIR) to analyze surface functional groups and X-ray diffraction (XRD) in studying structural characteristics. Differential Thermal Analysis (DTA) and Thermogravimetric Analysis (TGA) have been used to study the thermal properties of CNCs. Morphology of CNCs was studied using a Transmission Electron Microscope (TEM) and Scanning Electron Microscope (SEM). The crystallite size was found to be 10–50 nm using XRD data and the average particle size to be 221 nm using PSD analysis.     

Fluxgate magnetorelaxometry of superparamagnetic nanoparticles for hydrogel characterization

A new characterization method for hydrogels based on the relaxation behavior of superparamagnetic nanoparticles (MNPs) is proposed. MNPs are incorporated in the hydrogel to examine its network properties. By analyzing their relaxation behavior, incorporated and mobile nanoparticles can be studied. In the case of mobile nanoparticles, the microviscosity of the hydrogel can be determined. Thus, this method allows the studying of gelation as well as the degradation process of hydrogels. Furthermore, the hydrogel can have any shape (e.g. microspheres or larger blocks) and no sample preparation is needed, avoiding artefacts.     

Ultrasound-assisted dyeing of cellulose acetate

The possibility of reducing the use of auxiliaries in conventional cellulose acetate dyeing with Disperse Red 50 using ultrasound technique was studied as an alternative to the standard procedure. Dyeing of cellulose acetate yarn was carried out by using either mechanical agitation alone, with and without auxiliaries, or coupling mechanical and ultrasound agitation in the bath where the temperature range was maintained between 60 and 80 °C.The best results of dyeing kinetics were obtained with ultrasound coupled with mechanical agitation without auxiliaries (90% of bath exhaustion value at 80 °C). Hence the corresponding half dyeing times, absorption rate constants according to Cegarra–Puente modified equation and ultrasound efficiency were calculated confirming the synergic effect of sonication on the dyeing kinetics. Moreover the apparent activation energies were also evaluated and the positive effect of ultrasound added to mechanical agitation was evidenced by the lower value (48 kJ/mol) in comparison with 112 and 169 kJ/mol for mechanical stirring alone with auxiliaries and without, respectively.Finally, the fastness tests gave good values for samples dyed with ultrasound technique even without auxiliaries. Moreover color measurements on dyed yarns showed that the color yield obtained by ultrasound-assisted dyeing at 80 °C of cellulose acetate without using additional chemicals into the dye bath reached the same value yielded by mechanical agitation, but with remarkably shorter time.     

Ultrasound triggered cell death in vitro with doxorubicin loaded poly lactic-acid contrast agents

Traditional chemotherapy generally results in systemic toxicity, which also limits drug levels at the area of need. Two ultrasound contrast agents (UCA), with diameters between 1–2 μm in diameter and shell thicknesses of 100–200 nm, composed of poly lactic-acid (PLA), one loaded by surface adsorption and the other loaded by drug incorporation in the shell, were compared in vitro for potential use in cancer therapy. These poly lactic-acid (PLA) UCA platforms contain a gas core that in an ultrasound (US) field can cause the UCA to oscillate or rupture. Following a systemic injection of drug loaded UCA with external application of US focused at the area of interest, this platform could potentially increase drug toxicity at the area of need, while protecting healthy tissue through microencapsulation of the drug. In vitro toxicity in MDA-MB-231 breast cancer cells of the surface-adsorbed and shell-incorporated doxorubicin (Dox) loaded UCA were examined at 5 MHz insonation using a pulse repetition frequency of 100 Hz at varying pressure amplitudes. Both platforms resulted in equivalent cell death compared to free Dox and US when insonated at peak positive pressure amplitudes of 1.26 MPa and above. While no significant changes in cell death were seen for surface adsorbed Dox-UCA with or without insonation, cell death using the platform with Dox incorporated within the shell increased from 16.12% to 25.78% (p = 0.0272), approaching double the potency of the platform when insonated at peak positive pressure amplitudes of 1.26 MPa and above. This mechanism is believed to be the result of UCA rupture at higher insonation pressure amplitudes, resulting in more exposed drug and shell surface area as well as increased cellular uptake of Dox containing polymer shell fragments. This study has shown that a polymer UCA with drug housed within the shell may be used for US-triggered cell death. US activation can be used to make a carrier significantly more potent once in the area of need.     

Effects of ultrasonic conditions on the interfacial property and emulsifying property of cellulose nanoparticles from ginkgo seed shells

Cellulose microparticles from ginkgo seed shells were treated by ultrasonic treatments within the selected output powders (150–600 W) and durations (10–60 min) to produce cellulose nanoparticles. The main aim of this study was to investigate effects of ultrasonic conditions on the interfacial property and emulsifying property of those cellulose nanoparticles. Compared to ultrasonic output powers, ultrasonic durations showed the greater influence on morphology and physical properties of cellulose nanoparticles. Atomic force microscopy revealed that noodle-like cellulose particles with 1100 nm in length gradually became the short rod-like nanoparticles with 300 nm in length with increasing of ultrasonic duration from 10 min to 60 min. Moreover, results of contact angles indicated that ultrasound could significantly improve hydrophobicity of cellulose nanoparticles. The interfacial shear rheology showed that although all cellulose nanoparticles exhibited the similar interface adsorption behavior which showed the initial lag-phase of adsorption, followed by the interface saturation, the time of this initial lag-phase was affected by ultrasonic conditions. The increase of ultrasonic duration and ultrasonic power could shorten the time of this initial lag-phase, suggesting the resulting cellulose nanoparticles easier adsorption at the O/W interface. It was probably attributed to its small size and high hydrophobicity induced by intense ultrasonic treatments. Meanwhile, the cellulose nanoparticles with small size and higher hydrophobicity exhibited the better emulsifying ability to stabilize oil-in-water emulsions due to the formation of the viscoelastic interfacial film. This study improved understanding about changes in interfacial and emulsifying properties of cellulose nanoparticles caused by ultrasonic treatments.     

Acoustic-responsive carbon dioxide-loaded liposomes for efficient drug release

The role of liposomes as drug carriers has been investigated. Ultrasound-based drug release methods have been developed for on-demand drug delivery. However, the acoustic responses of current liposome carriers result in low drug release efficiency. In this study, CO₂-loaded liposomes were synthesized under high pressure from supercritical CO₂ and irradiated with ultrasound at 237 kHz to demonstrate their superior acoustic responsiveness. When liposomes containing fluorescent drug models were irradiated with ultrasound under acoustic pressure conditions that are safe for the human body, CO₂-loaded liposomes synthesized using supercritical CO₂ had 17.1 times higher release efficiency than liposomes synthesized using the conventional Bangham method. In particular, the release efficiency of CO₂-loaded liposomes synthesized using supercritical CO₂ and monoethanolamine was 19.8 times higher than liposomes synthesized using the conventional Bangham method. These findings on the release efficiency of acoustic-responsive liposomes suggest an alternative liposome synthesis strategy for on-demand release of drugs by ultrasound irradiation in future therapies.     

Influence of ultrasound treatment on accessibility and regioselective oxidation reactivity of cellulose

Cellulose fibers were treated with ultrasound in order to improve the accessibility and the reactivity of cellulose. The influence of ultrasound treatment on changes of morphology structure, accessibility and oxidation reactivity of cellulose with sodium periodate were discussed. The results revealed an increase in cellulose’s accessibility in terms of water retention value (WRV) with increasing ultrasound treatment time, corresponding to 73.0%, 75.6%, 80.8%, 98.7% and 119.0% after treated for 0, 90, 180, 360 and 720 s, respectively. Furthermore, the regioselective oxidation reactivity of cellulose with sodium periodate was also successfully improved by the ultrasound treatment. However, no significant changes in crystallinity of cellulose were noted after ultrasound treatment. The oxidized products dialdehyde cellulose (DAC) was further characterized by means of FTIR, X-ray diffraction and SEM.     

Ultrasound mediated destruction of multifunctional microbubbles for image guided delivery of oxygen and drugs

We synthesized multifunctional activatible microbubbles (MAMs) for ultrasound mediated delivery of oxygen and drugs with both ultrasound and fluorescence imaging guidance. Oxygen enriched perfluorocarbon (PFC) compound was encapsulated in liposome microbubbles (MBs) by a modified emulsification process. DiI dye was loaded as a model drug. The ultrasound targeted microbubble destruction (UTMD) process was guided by both ultrasonography and fluorescence imaging modalities. The process was validated in both a dialysis membrane tube model and a porcine carotid artery model. Our experiment results show that the UTMD process effectively facilitates the controlled delivery of oxygen and drug at the disease site and that the MAM agent enables ultrasound and fluorescence imaging guidance of the UTMD process. The proposed MAM agent can be potentially used for UTMD-mediated combination therapy in hypoxic ovarian cancer.     

Stable and transient bubble formation in acoustically-responsive scaffolds by acoustic droplet vaporization: theory and application in sequential release

Acoustically-responsive scaffolds (ARSs), which are fibrin hydrogels containing monodispersed perfluorocarbon (PFC) emulsions, respond to ultrasound in an on-demand, spatiotemporally-controlled manner via a mechanism termed acoustic droplet vaporization (ADV). Previously, ADV has been used to control the release of bioactive payloads from ARSs to stimulate regenerative processes. In this study, we used classical nucleation theory (CNT) to predict the nucleation pressure in emulsions of different PFC cores as well as the corresponding condensation pressure of the ADV-generated bubbles. According to CNT, the threshold bubble radii above which ADV-generated bubbles remain stable against condensation were 0.4 µm and 5.2 µm for perfluoropentane (PFP) and perfluorohexane (PFH) bubbles, respectively, while ADV-generated bubbles of any size in perfluorooctane (PFO) condense back to liquid at ambient condition. Additionally, consistent with the CNT findings, stable bubble formation from PFH emulsion was experimentally observed using confocal imaging while PFO emulsion likely underwent repeated vaporization and recondensation during ultrasound pulses. In further experimental studies, we utilized this unique feature of ADV in generating stable or transient bubbles, through tailoring the PFC core and ultrasound parameters (excitation frequency and pulse duration), for sequential delivery of two payloads from PFC emulsions in ARSs. ADV-generated stable bubbles from PFH correlated with complete release of the payload while transient ADV resulted in partial release, where the amount of payload release increased with the number of ultrasound exposure. Overall, these results can be used in developing drug delivery strategies using ARSs.     

One injection for one-week controlled release: In vitro and in vivo assessment of ultrasound-triggered drug release from injectable thermoresponsive biocompatible hydrogels

Episodic release of bioactive compounds is often necessary for appropriate biological effects under specific physiological conditions. Here, we aimed to develop an injectable, biocompatible, and thermosensitive hydrogel system for ultrasound (US)-triggered drug release. An mPEG-PLGA-BOX block copolymer hydrogel was synthesized. The viscosity of 15 wt% hydrogel is 0.03 Pa*s at 25 °C (liquid form) and 34.37 Pa*s at 37 °C (gel form). Baseline and US-responsive in vitro release profile of a small molecule (doxorubicin) and that of a large molecule (FITC-dextran), from the hydrogel, was tested. A constant baseline release was observed in vitro for 7 d. When triggered by US (1 MHz, continuous, 0.4 W/cm²), the release rate increased by approximately 70 times. Without US, the release rate returned to baseline. Baseline and US-responsive in vivo release profile of doxorubicin was tested by subcutaneous injection in the back of mice and rats. Following injection into the subcutaneous layer, in vivo results also suggested that the hydrogels remained in situ and provided a steady release for at least 7 d; in the presence of the US-trigger, in vivo release from the hydrogel increased by approximately 10 times. Therefore, the mPEG-PLGA-BOX block copolymer hydrogel may serve as an injectable, biocompatible, and thermosensitive hydrogel system that is applicable for US-triggered drug release.     

Comparison of two different ultrasound reactors for the treatment of cellulose fibers

The pulp and paper industry is in continuous need for energy-efficient production processes. In the refining process of mechanical pulp, fibrillation is one of the essential unit operations that count for up to 80% of the total energy use. This initial study explores the potential and development of new type of scalable ultrasound reactor for energy efficient mechanical pulping. The developed reactor is of continuous flow type and based on both hydrodynamic and acoustic cavitation in order to modify the mechanical properties of cellulose fibers. A comparison of the prototype tube reactor is made with a batch reactor type where the ultrasonic horn is inserted in the fluid. The pulp samples were sonicated by high-intensity ultrasound, using tuned sonotrodes enhancing the sound pressure and cavitation intensity by a controlled resonance in the contained fluid. The resonant frequency of the batch reactor is 20.8 kHz and for the tube reactor it is 22.8 kHz. The power conversion efficiency for the beaker setup is 25% and 36% in case of the tube reactor in stationary mode. The objective is to verify the benefit of resonance enhanced cavitation intensity when avoiding the effect of Bjerkenes forces. The setup used enables to keep the fibers in the pressure antinodes of the contained fluid. In case of the continuous flow reactor the effect of hydrodynamic cavitation is also induced. The intensity of the ultrasound in both reactors was found to be high enough to produce cavitation in the fluid suspension to enhance the fiber wall treatment. Results show that the mechanical properties of the fibers were changed by the sonification in all tests. The continuous flow type was approximately 50% more efficient than the beaker. The effect of keeping fibers in the antinode of the resonant mode shape of the irradiation frequency was also significant. The effect on fiber properties for the tested mass fraction was determined by a low-intensity ultrasound pulse-echo based measurement method, and by a standard pulp analyzer.     

Progress and problems in the application of focused ultrasound for blood-brain barrier disruption

Advances in neuroscience have resulted in the development of new diagnostic and therapeutic agents for potential use in the central nervous system (CNS). However, the ability to deliver the majority of these agents to the brain is limited by the blood-brain barrier (BBB), a specialized structure of the blood vessel wall that hampers transport and diffusion from the blood to the brain. Many CNS disorders could be treated with drugs, enzymes, genes, or large-molecule biotechnological products such as recombinant proteins, if they could cross the BBB. This article reviews the problems of the BBB presence in treating the vast majority of CNS diseases and the efforts to circumvent the BBB through the design of new drugs and the development of more sophisticated delivery methods. Recent advances in the development of noninvasive, targeted drug delivery by MRI-guided ultrasound-induced BBB disruption are also summarized.     

Preparation and in vitro evaluation of an ultrasound-triggered drug delivery system: 10-hydroxycamptothecin loaded PLA microbubbles

10-Hydroxycamptothecin (HCPT) loaded PLA microbubbles, used as an ultrasound-triggered drug delivery system, were fabricated by a double emulsion-solvent evaporation method. The obtained microbubbles were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and confocal laser scanning microscope (CLSM). In addition, the effect of diagnostic ultrasound exposure on BEL-7402 cells combined with HCPT-loaded PLA microbubbles was evaluated using cytotoxicity assay, CLSM and flow cytometry (FCM). It was found that the HCPT-loaded PLA microbubbles showed smooth surface and spherical shape, and the drug was amorphously dispersed within the shell and the drug loading content reached up to 1.69%. Nearly 20% of HCPT was released upon exposure to diagnostic ultrasound at frequency of 3.5 MHz for 10 min. Moreover, HCPT fluorescence in the cells treated only with the HCPT-loaded PLA microbubbles was discernible, but less intense, while those treated with the microbubbles in conjunction with ultrasound exposure was evident and intense, indicating an increased cellular uptake of HCPT by ultrasound exposure. Cytotoxicity test on BEL-7402 cells indicated that the HCPT-loaded PLA microbubbles combined with ultrasound exposure were more cytotoxic than the microbubbles alone. The results suggest that the combination of drug loaded PLA microbubbles and diagnostic ultrasound exposure exhibit an effective intracellular drug uptake by tumor cells, indicating their great potential for antitumor therapy.     

Recent ultrasound advancements for the manipulation of nanobiomaterials and nanoformulations for drug delivery

Recent advances in ultrasound (US) have shown its great potential in biomedical applications as diagnostic and therapeutic tools. The coupling of US-assisted drug delivery systems with nanobiomaterials possessing tailor-made functions has been shown to remove the limitations of conventional drug delivery systems. The low-frequency US has significantly enhanced the targeted drug delivery effect and efficacy, reducing limitations posed by conventional treatments such as a limited therapeutic window. The acoustic cavitation effect induced by the US-mediated microbubbles (MBs) has been reported to replace drugs in certain acute diseases such as ischemic stroke. This review briefly discusses the US principles, with particular attention to the recent advancements in drug delivery applications. Furthermore, US-assisted drug delivery coupled with nanobiomaterials to treat different diseases (cancer, neurodegenerative disease, diabetes, thrombosis, and COVID-19) are discussed in detail. Finally, this review covers the future perspectives and challenges on the applications of US-mediated nanobiomaterials.     

Multi-time scale characterization of acoustic droplet vaporization and payload release of phase-shift emulsions using high-speed microscopy

Acoustic droplet vaporization (ADV) is the phase-transitioning of perfluorocarbon emulsions, termed phase-shift emulsions, into bubbles using focused ultrasound. ADV has been utilized in many biomedical applications. For localized drug release, phase-shift emulsions with a bioactive payload can be incorporated within a hydrogel to yield an acoustically-responsive scaffold (ARS). The dynamics of ADV and associated drug release within hydrogels are not well understood. Additionally, emulsions used in ARSs often contain high molecular weight perfluorocarbons, which is unique relative to other ADV applications. In this study, we used ultra-high-speed brightfield and fluorescence microscopy, at frame rates up to 30 million and 0.5 million frames per second, respectively, to elucidate ADV dynamics and payload release kinetics in fibrin-based ARSs containing phase-shift emulsions with three different perfluorocarbons: perfluoropentane (PFP), perfluorohexane (PFH), and perfluorooctane (PFO). At an ultrasound excitation frequency of 2.5 MHz, the maximum expansion ratio, defined as the maximum bubble diameter during ADV normalized by the initial emulsion diameter, was 4.3 ± 0.8, 4.1 ± 0.6, and 3.6 ± 0.4, for PFP, PFH, PFO emulsions, respectively. ADV yielded stable bubble formation in PFP and PFH emulsions, though the bubble growth rate post-ADV was three orders of magnitudes slower in the latter emulsion. Comparatively, ADV generated bubbles in PFO emulsions underwent repeated vaporization/recondensation or fragmentation. Different ADV-generated bubble dynamics resulted in distinct release kinetics in phase-shift emulsions carrying fluorescently-labeled payloads. The results provide physical insight enabling the modulation of bubble dynamics with ADV and hence release kinetics, which can be used for both diagnostic and therapeutic applications of ultrasound.