https://scholars.lib.ntu.edu.tw/handle/123456789/633789
標題: | Combined use of microbubbles of various sizes and single-transducer dual-frequency ultrasound for safe and efficient inner ear drug delivery | 作者: | Liao, Ai Ho Wang, Chih Hung Wang, Bo Han Lin, Yi Chun Chuang, Ho Chiao HAO-LI LIU Shih, Cheng Ping |
關鍵字: | cavitation | drug delivery | dual-frequency ultrasound | hair cell | inner ear | insulin-like growth factor 1 (IGF-1) | microbubbles | round window membrane | 公開日期: | 1-一月-2022 | 來源出版物: | Bioengineering and Translational Medicine | 摘要: | We have previously applied ultrasound (US) with microbubbles (MBs) to enhance inner ear drug delivery, with most experiments conducted using single-frequency, high-power density US, and multiple treatments. In the present study, the treatment efficacy was enhanced and safety concerns were addressed using a combination of low-power-density, single-transducer, dual-frequency US (ISPTA = 213 mW/cm2) and MBs of different sizes coated with insulin-like growth factor 1 (IGF-1). This study is the first to investigate the drug-coating capacity of human serum albumin (HSA) MBs of different particle sizes and their drug delivery efficiency. The concentration of HSA was adjusted to produce different MB sizes. The drug-coating efficiency was significantly higher for large-sized MBs than for smaller MBs. In vitro Franz diffusion experiments showed that the combination of dual-frequency US and large MB size delivered the most IGF-1 (24.3 ± 0.47 ng/cm2) to the receptor side at the second hour of treatment. In an in vivo guinea pig experiment, the efficiency of IGF-1 delivery into the inner ear was 15.9 times greater in animals treated with the combination of dual-frequency US and large MBs (D-USMB) than in control animals treated with round window soaking (RWS). The IGF-1 delivery efficiency was 10.15 times greater with the combination of single-frequency US and large size MBs (S-USMB) than with RWS. Confocal microscopy of the cochlea showed a stronger distribution of IGF-1 in the basal turn in the D-USMB and S-USMB groups than in the RWS group. In the second and third turns, the D-USMB group showed the greatest IGF-1 distribution. Hearing assessments revealed no significant differences among the D-USMB, S-USMB, and RWS groups. In conclusion, the combination of single-transducer dual-frequency US and suitably sized MBs can significantly reduce US power density while enhancing the delivery of large molecular weight drugs, such as IGF-1, to the inner ear. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/633789 | ISSN: | 2380-6761 | DOI: | 10.1002/btm2.10450 |
顯示於: | 電機工程學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。