Enhanced delivery to brain using sonosensitive liposome and microbubble with focused ultrasound

Hyungwon Moon, Kihwan Hwang, Kyung Mi Nam, Yoon Seok Kim, Min Jung Ko, Hyun Ryoung Kim, Hak Jong Lee, Mi Jeong Kim, Tae Ho Kim, Kyung Sun Kang, Nam Gyo Kim, Soon Won Choi, Chae Yong Kim

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Glioblastoma is considered one of the most aggressive and dangerous brain tumors. However, treatment of GBM has been still challenged due to blood-brain barrier (BBB). BBB prevents that the chemotherapeutic molecules are extravasated to brain. In this study, sonosensitive liposome encapsulating doxorubicin (DOX) was developed for enhancement of GBM penetration in combination with focused ultrasound (FUS) and microbubbles. Upon ultrasound (US) irradiation, microbubbles induce cavitation resulting in the tight junction of BBB endothelium to temporarily open. In addition, the composition of sonosensitive liposome was optimized by comparison of sonosensitivity and intracellular uptake to U87MG cells. The optimal sonosensitive liposome, IMP301-DC, resulted 123.9 ± 38.2 nm in size distribution and 98.2 % in loading efficiency. Related to sonosensitivity of IMP301-DC, US-triggered release ratio of doxorubicin was 69.2 ± 12.3 % at 92 W/cm2 of US intensity for 1 min. In the in vivo experiments, the accumulation of DiD fluorescence probe labeled IMP301-DC-shell in the brain through the BBB opening was increased more than two-fold compared to that of Doxil-shell, non-sonosensitive liposome. US exposure significantly increased GBM cytotoxicity of IMP301-DC. In conclusion, this study demonstrated that IMP301-DC could serve as an alternative solution to enhance the penetration to GBM treatment via BBB opening by non-invasive FUS combined with microbubbles.

Original languageEnglish
Article number213102
JournalBiomaterials Advances
Volume141
DOIs
StatePublished - Oct 2022

Keywords

  • Blood-brain barrier
  • Doxorubicin
  • Focused ultrasound
  • Glioblastoma
  • Microbubble
  • Sonosensitive liposome

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