Ultrasound and Microbubbles Enhance Uptake of Doxorubicin in Murine Kidneys

Eikrem, Øystein; Kotopoulis, Spiros; Popa, M; Safont, Mireia Mayoral; Fossan, Kjell Ove; Leh, Sabine; Landolt, Lea; Bábíčková, Janka; Gudbrandsen, Oddrun Anita; Gilja, Odd Helge; Riedel, Bettina; Schjøtt, Jan; McCormack, Emmet; Marti, Hanspeter

doi:10.3390/pharmaceutics13122038

Cited by 3 publications

(1 citation statement)

References 45 publications

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“…Previously, we showed in vivo that using ultrasound alone at similar acoustic settings resulted in significant increase in drug uptake in mouse kidneys (healthy tissue) [61]. This was not observed here and may be due to the difference in cell line and response to stresses, or the lack of correlation between in vitro experiments and healthy tissue in vivo.…”

Section: In Vitro Experimentscontrasting

confidence: 46%

SonoVue® vs. Sonazoid™ vs. Optison™: Which Bubble Is Best for Low-Intensity Sonoporation of Pancreatic Ductal Adenocarcinoma?

et al. 2022

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The use of ultrasound and microbubbles to enhance therapeutic efficacy (sonoporation) has shown great promise in cancer therapy from in vitro to ongoing clinical studies. The fastest bench-to-bedside translation involves the use of ultrasound contrast agents (microbubbles) and clinical diagnostic scanners. Despite substantial research in this field, it is currently not known which of these microbubbles result in the greatest enhancement of therapy within the applied conditions. Three microbubble formulations—SonoVue®, Sonazoid™, and Optison™—were physiochemically and acoustically characterized. The microbubble response to the ultrasound pulses used in vivo was simulated via a Rayleigh–Plesset type equation. The three formulations were compared in vitro for permeabilization efficacy in three different pancreatic cancer cell lines, and in vivo, using an orthotopic pancreatic cancer (PDAC) murine model. The mice were treated using one of the three formulations exposed to ultrasound from a GE Logiq E9 and C1-5 ultrasound transducer. Characterisation of the microbubbles showed a rapid degradation in concentration, shape, and/or size for both SonoVue® and Optison™ within 30 min of reconstitution/opening. Sonazoid™ showed no degradation after 1 h. Attenuation measurements indicated that SonoVue® was the softest bubble followed by Sonazoid™ then Optison™. Sonazoid™ emitted nonlinear ultrasound at the lowest MIs followed by Optison™, then SonoVue®. Simulations indicated that SonoVue® would be the most effective bubble using the evaluated ultrasound conditions. This was verified in the pre-clinical PDAC model demonstrated by improved survival and largest tumor growth inhibition. In vitro results indicated that the best microbubble formulation depends on the ultrasound parameters and concentration used, with SonoVue® being best at lower intensities and Sonazoid™ at higher intensities.

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Section: In Vitro Experimentscontrasting

confidence: 46%

SonoVue® vs. Sonazoid™ vs. Optison™: Which Bubble Is Best for Low-Intensity Sonoporation of Pancreatic Ductal Adenocarcinoma?

et al. 2022

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In Vitro Evaluation of Ultrasound Effectiveness in Controlling Doxorubicin Release from Albumin-Conjugated Liposomes

Abuwatfa

Paul

AlSawaftah

et al. 2022

j biomed nanotechnol

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Functionalized liposomes are among the most promising antineoplastic agents delivery vehicles. Contemporaneous to their accretion at the tumor site, they need to be potentiated to release their cargo using a suitable triggering modality. In this work, targeted Doxorubicin (DOX)-loaded stealth liposomes were synthesized and functionalized with Human Serum Albumin (HSA) to target the overexpressed HSA receptors (HSA-Rs). The effects of low-frequency ultrasound (LFUS) in inducing DOX release from the synthesized liposomes were investigated In Vitro. DOX release increased with the increasing power density of ultrasound. HSA conjugation to the liposomes increased their sensitivity to LFUS. Furthermore, HSA conjugation also enhanced the liposome’s cytotoxic activity and uptake by the cancer cells overexpressing HSA-Rs. This cytotoxic activity and cellular uptake were further enhanced by triggering drug release from those targeted liposomes using LFUS. Combining HSA-targeted liposomes with LFUS is a promising approach in drug delivery.

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Ultrasound stimulated microbubbles cavitation enhanced the therapeutic effect of colchicine in rats with acute gouty arthritis

Zhang,

Bo,

Wang

et al. 2024

Preprint

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Objective To investigate whether cavitation induced by ultrasound stimulated microbubbles (USMB) can enhance the therapeutic effect of colchicine and reduce its side effects on acute gouty arthritis (AGA) in rats. Materials and Methods Each rat underwent right ankle joint contrast-enhanced ultrasound (CEUS) before and following cavitation treatment. The area under the curve (AUC) of CEUS before and after cavitation and among groups were compared to contrast the impact on blood perfusion of the ankle joint in rats with cavitation. The symptoms of AGA were evaluated based on 24-hour ankle joint swelling degree and gait score. The infiltration of neutrophils was assessed using the Hematoxylin-eosin(HE)staining, while the inflammation and dilation of blood vessels were measured by and plasma interleukin-1β (IL-1β) and endothelial nitric oxide synthase (eNOS). Moreover, the magnitude of side effects was analyzed by gastrointestinal reaction score. Results The AUC after cavitation induced by USMB were significantly higher than those before cavitation. When compared with groups without cavitation, the AUC were markedly higher in groups treated with cavitation (all p<0.01). In groups treated with cavitation combined with colchicine, the degree of ankle swelling, gait scores, and the level of plasma IL-1β in AGA rats were lower, while the concentration of plasma eNOS was higher, group treated with colchicine alone (all p<0.05). HE staining showed that cavitation combined with colchicine helped to reduce the neutrophil synovial infiltration of ankle joint and decrease the gastrointestinal reaction score in rats with AGA. Compared with the three groups receiving drug treatment, the incidence of gastrointestinal reaction score in the low concentration group was significantly lower than that in the high concentration groups (all p<0.05). Conclusion The cavitation induced by USMB could significantly enhance the blood perfusion of ankle joint in rats with AGA, leading to the increase in therapeutic effect of colchicine and reduce the dose used of colchicine, thus minimizing the side effects associated with it.

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Ultrasound and Microbubbles Enhance Uptake of Doxorubicin in Murine Kidneys

Cited by 3 publications

References 45 publications

SonoVue® vs. Sonazoid™ vs. Optison™: Which Bubble Is Best for Low-Intensity Sonoporation of Pancreatic Ductal Adenocarcinoma?

SonoVue® vs. Sonazoid™ vs. Optison™: Which Bubble Is Best for Low-Intensity Sonoporation of Pancreatic Ductal Adenocarcinoma?

In Vitro Evaluation of Ultrasound Effectiveness in Controlling Doxorubicin Release from Albumin-Conjugated Liposomes

Ultrasound stimulated microbubbles cavitation enhanced the therapeutic effect of colchicine in rats with acute gouty arthritis

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