Formulation and characterisation of drug-loaded antibubbles for image-guided and ultrasound-triggered drug delivery

Kotopoulis, Spiros; Lam, Ching‐Wan; Haugse, Ragnhild; Snipstad, Sofie; Murvold, Elisa Thodesen; Jouleh, Tæraneh; Berg, Sigrid; Hansen, Rune; Popa, Mihaela; Cormack, Emmet Mc; Gilja, Odd Helge; Poortinga, Albert T.

doi:10.1016/j.ultsonch.2022.105986

Cited by 14 publications

(11 citation statements)

References 46 publications

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“…According to the MTT cell toxicity assay results (Figure b), all MB samples did not reduce the viability of MRC-5 cells up to a concentration of 2.5 × 10 7 MBs/mL after 72 h of incubation. Concentrations of ∼1–2 × 10 7 MBs/mL are typically used for in vitro and in vivo experiments in the literature. − With an increase in the concentration of MBs to 5 × 10 7 MBs/mL, cell viability was above 80%, suggesting that MBs have a negligible effect on cells’ viability. All samples demonstrated standard deviation samples without statistical significance between pure BSA shell and hybrid “protein–copolymer” shell compositions, confirming biocompatibility of presented MBs produced with the BSA@P(VP-AA) “protein–copolymer” complex.…”

Section: Results and Discussionmentioning

confidence: 99%

Hybrid (Bovine Serum Albumin)/Poly(N-vinyl-2-pyrrolidone-co-acrylic acid)-Shelled Microbubbles as Advanced Ultrasound Contrast Agents

Estifeeva

Barmin

Rudakovskaya

et al. 2022

ACS Appl. Bio Mater.

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Microbubbles are routinely used ultrasound contrast agents in the clinic. While a soft protein shell is commercially preferable for imaging purposes, a rigid polymer shell demonstrates prolonged agent stability. Hence, combining polymers and proteins in one shell composition can advance microbubble properties. We formulated the hybrid “protein–copolymer” microbubble shell with a complex of bovine serum albumin and an amphiphilic copolymer of N-vinyl-2-pyrrolidone and acrylic acid. The resulting microbubbles demonstrated advanced physicochemical and acoustic properties, preserving in vitro biocompatibility. Adjusting the mass ratio between protein and copolymer allowed fine tuning of the microbubble properties of concentration (by two orders, up to 1010 MBs/mL), mean size (from 0.8 to 5 μm), and shell thickness (from 28 to 50 nm). In addition, the minimum air–liquid surface tension for the “protein–copolymer” solution enabled the highest bubble concentration. At the same time, a higher copolymer amount in the bubble shell increased the bubble size and tuned duration and intensity of the contrast during an ultrasound procedure. Demonstrated results exemplify the potential of the hybrid “protein–polymer” microbubble shell, allowing tailoring of microbubble properties for image-guided applications, combining advances of each material involved in the formulation.

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Section: Results and Discussionmentioning

confidence: 99%

Hybrid (Bovine Serum Albumin)/Poly(N-vinyl-2-pyrrolidone-co-acrylic acid)-Shelled Microbubbles as Advanced Ultrasound Contrast Agents

Estifeeva

Barmin

Rudakovskaya

et al. 2022

ACS Appl. Bio Mater.

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“…Ultrasonography was applied to induce release of an anticancer drug, adriamycin (ADM) from adriamycin gelatin nanogel modified with fluoride anion (ADM-GNMF) [ 190 ]. Moreover, ultrasound guidance can dramatically enhance the drug delivery efficiency [ 191 , 192 ]. Ultrasound-induced cationic nanodroplets with variable sizes have been shown to enhance tissue and cell permeability [ 193 ].…”

Section: Strategies To Improve Drug Penetration Into Solid Tumorsmentioning

confidence: 99%

Enhancing drug penetration in solid tumors via nanomedicine: Evaluation models, strategies and perspectives

Shen,

Pan,

Gong

et al. 2024

Bioactive Materials

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“…Lipid shell microbubbles with longer lipid chains have longer in vivo half-life 25 and potentially higher delivery efficiency for larger molecules, but optimal acoustic conditions for delivery are not well-defined 26 . A formulation of 'antibubbles,” comprising liquid droplets surrounded by a gas layer has been described, may allow large volumes of payload to be carried by the internal droplets, but is in very early proof of concept testing stages 27 . Drug-loaded nanoparticles linked to the microbubble shell have been described 28 , 29 .…”

Section: Introductionmentioning

confidence: 99%

Ultrasound enhanced siRNA delivery using cationic liposome-microbubble complexes for the treatment of squamous cell carcinoma

Qin,

Chen,

Zhu

et al. 2024

Nanotheranostics

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Rationale: Microbubble ( MB ) contrast agents combined with ultrasound targeted microbubble cavitation ( UTMC ) are a promising platform for site-specific therapeutic oligonucleotide delivery. We investigated UTMC-mediated delivery of siRNA directed against epidermal growth factor receptor ( EGFR ), to squamous cell carcinoma ( SCC ) via a novel MB-liposome complex ( LPX ). Methods: LPXs were constructed by conjugation of cationic liposomes to the surface of C 4 F 10 gas-filled lipid MBs using biotin/avidin chemistry, then loaded with siRNA via electrostatic interaction. Luciferase-expressing SCC-VII cells ( SCC-VII-Luc ) were cultured in Petri dishes. The Petri dishes were filled with media in which LPXs loaded with siRNA against firefly luciferase ( Luc siRNA ) were suspended. Ultrasound ( US ) (1 MHz, 100-µs pulse, 10% duty cycle) was delivered to the dishes for 10 sec at varying acoustic pressures and luciferase assay was performed 24 hr later. In vivo siRNA delivery was studied in SCC-VII tumor-bearing mice intravenously infused with a 0.5 mL saline suspension of EGFR siRNA LPX (7×10 8 LPX, ~30 µg siRNA) for 20 min during concurrent US (1 MHz, 0.5 MPa spatial peak temporal peak negative pressure, five 100-µs pulses every 1 ms; each pulse train repeated every 2 sec to allow reperfusion of LPX into the tumor). Mice were sacrificed 2 days post treatment and tumor EGFR expression was measured (Western blot). Other mice ( n =23) received either EGFR siRNA-loaded LPX + UTMC or negative control ( NC ) siRNA-loaded LPX + UTMC on days 0 and 3, or no treatment (“sham”). Tumor volume was serially measured by high-resolution 3D US imaging. Results: Luc siRNA LPX + UTMC caused significant luciferase knockdown vs. no treatment control, p <0.05) in SCC-VII-Luc cells at acoustic pressures 0.25 MPa to 0.9 MPa, while no significant silencing effect was seen at lower pressure (0.125 MPa). In vivo, EGFR siRNA LPX + UTMC reduced tumor EGFR expression by ~30% and significantly inhibited tumor growth by day 9 (~40% decrease in tumor volume vs. NC siRNA LPX + UTMC, p <0.05). Conclusions: Luc siRNA LPXs + UTMC achieved functional delivery of Luc siRNA to SCC-VII-Luc cells in vitro . EGFR siRNA LPX + UTMC inhibited tumor growth and suppressed EGFR expression in vivo , suggesting that this platform holds promise for non-invasive, image-guided targeted delivery of therapeutic siRNA for cancer treatment.

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Formulation and characterisation of drug-loaded antibubbles for image-guided and ultrasound-triggered drug delivery

Cited by 14 publications

References 46 publications

Hybrid (Bovine Serum Albumin)/Poly(N-vinyl-2-pyrrolidone-co-acrylic acid)-Shelled Microbubbles as Advanced Ultrasound Contrast Agents

Hybrid (Bovine Serum Albumin)/Poly(N-vinyl-2-pyrrolidone-co-acrylic acid)-Shelled Microbubbles as Advanced Ultrasound Contrast Agents

Enhancing drug penetration in solid tumors via nanomedicine: Evaluation models, strategies and perspectives

Ultrasound enhanced siRNA delivery using cationic liposome-microbubble complexes for the treatment of squamous cell carcinoma

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