Campbell Christopher K, O'Brien Kirsten, Kosk Dariusz, Rumney Robin M H, Glynne-Jones Peter, Birkin Peter R, LuTheryn Gareth, Webb Jeremy S, Stride Eleanor, Carugo Dario, Evans Nicholas D
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK.
Bone and Joint Research Group, Faculty of Medicine, University of Southampton, Southampton, UK; School of Engineering, University of Southampton, Southampton, UK.
Ultrason Sonochem. 2025 Jul;118:107332. doi: 10.1016/j.ultsonch.2025.107332. Epub 2025 Apr 9.
Perfluorocarbon nanodroplets (PFC-NDs) are promising ultrasound-responsive theranostic agents with applications in both diagnostic imaging and drug delivery. The acoustic vaporisation threshold, extravasation potential, and stability of PFC-NDs are all affected by their size. However, methods to ensure reproducible size and concentration during production by sonication are lacking. To address this need, we examined the effect of temperature, sonication time, sonication intensity, PFC concentration and sonicator tip height on ND characteristics. PFC-NDs with a perfluoro-n-pentane (PFP) core and a phospholipid shell were manufactured by probe-sonication. Pulsed sonication was used to maintain the sample temperature below the boiling point of PFP. Median particle diameter was measured using nanoparticle tracking analysis. PFC-ND diameter increased with increasing PFP concentration, with a stronger relationship as sonicator tip height increased. Above 5% v/v PFP, there was a qualitative increase in the number of particles visible by light microscopy. Increasing the sonication duration did not yield a significant change in ND size. A minimum amplitude of 60% was required for mixing to occur, with amplitudes of 80% and 100% resulting in foam production. Sonicator power output was linear with respect to time but differed depending on sample volume, composition, and vessel geometry. This study indicates that controlling the processing parameters can facilitate reproducible manufacturing of PFC-NDs.
全氟碳纳米液滴（PFC-NDs）是很有前景的超声响应型诊疗试剂，可应用于诊断成像和药物递送。PFC-NDs的声汽化阈值、渗出潜力和稳定性均受其尺寸影响。然而，目前缺乏在超声处理生产过程中确保尺寸和浓度可重现的方法。为满足这一需求，我们研究了温度、超声处理时间、超声强度、PFC浓度和超声探头高度对纳米液滴特性的影响。采用探针超声法制备了具有全氟正戊烷（PFP）核和磷脂壳的PFC-NDs。采用脉冲超声处理以将样品温度维持在PFP沸点以下。使用纳米颗粒跟踪分析测量中位粒径。PFC-ND直径随PFP浓度增加而增大，随着超声探头高度增加，这种关系更强。当PFP体积分数超过5%时，光学显微镜下可见的颗粒数量有定性增加。增加超声处理持续时间并未使纳米液滴尺寸产生显著变化。发生混合所需的最小振幅为60%，80%和100%的振幅会产生泡沫。超声功率输出随时间呈线性变化，但因样品体积、组成和容器几何形状而异。本研究表明，控制加工参数有助于可重现地制造PFC-NDs。
