High-Speed Optical Characterization of Protein-and-Nanoparticle-Stabilized Microbubbles for Ultrasound-Triggered Drug Release

被引:0
作者
Nawijn, Charlotte L. [1 ]
Segers, Tim [2 ]
Lajoinie, Guillaume [1 ]
Berg, Sigrid [3 ]
Snipstad, Sofie [4 ,5 ,6 ]
Davies, Catharina de Lange [6 ]
Versluis, Michel [1 ]
机构
[1] Univ Twente, Tech Med TechMed Ctr, Phys Fluids Grp, Enschede, Netherlands
[2] Univ Twente, BIOS Lab Chip Grp, MESA Inst Nanotechnol, Max Planck Ctr Complex Fluid Dynam, Enschede, Netherlands
[3] SINTEF Digital, Dept Hlth Res, Trondheim, Norway
[4] SINTEF Ind, Dept Biotechnol & Nanomed, Trondheim, Norway
[5] St Olavs Hosp, Canc Clin, Trondheim, Norway
[6] Norwegian Univ Sci & Technol, Dept Phys, Trondheim, Norway
基金
荷兰研究理事会;
关键词
Ultrasound; Drug delivery; Microbubbles; Nanoparticles; Loaded microbubbles; Nanomedicine; High-speed imaging; Bright-field microscopy; Fluorescence microscopy; MEDIATED DELIVERY; CONTRAST AGENTS; SONOPORATION; OSCILLATIONS; BUBBLES; GENE;
D O I
10.1016/j.ultrasmedbio.2024.03.011
中图分类号
O42 [声学];
学科分类号
070206 ; 082403 ;
摘要
Objective: Ultrasound-triggered bubble-mediated local drug delivery has shown potential to increase therapeutic efficacy and reduce systemic side effects, by loading drugs into the microbubble shell and triggering delivery of the payload on demand using ultrasound. Understanding the behavior of the microbubbles in response to ultrasound is crucial for efficient and controlled release. Methods: In this work, the response of microbubbles with a coating consisting of poly(2-ethyl-butyl cyanoacrylate) (PEBCA) nanoparticles and denatured casein was characterized. High-speed recordings were taken of single microbubbles, in both bright field and fluorescence. Results: The nanoparticle-loaded microbubbles show resonance behavior, but with a large variation in response, revealing a substantial interbubble variation in mechanical shell properties. The probability of shell rupture and the probability of nanoparticle release were found to strongly depend on microbubble size, and the most effective size was inversely proportional to the driving frequency. The probabilities of both rupture and release increased with increasing driving pressure amplitude. Rupture of the microbubble shell occurred after fewer cycles of ultrasound as the driving pressure amplitude or driving frequency was increased. Conclusion: The results highlight the importance of careful selection of the driving frequency, driving pressure amplitude and duration of ultrasound to achieve the most efficient ultrasound-triggered shell rupture and nano- particle release of protein-and-nanoparticle-stabilized microbubbles.
引用
收藏
页码:1099 / 1107
页数:9
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