Release of vascular agonists from liposome-microbubble conjugate by ultrasound-mediated microbubble destruction: effect on vascular function

Carlos A. Franco-Urquijo, J. Ángel Navarro-Becerra, Amelia Ríos, Bruno Alfonso Escalante Acosta

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Abstract: The endothelium is a single cell layer of the vessel wall and a key regulator of blood flow in vascular beds. Local and systemic pathologies have been associated with alterations in endothelial function. However, targeting the endothelium with vasoconstrictor or vasodilator drugs is often accompanied by systemic effects. Here, we evaluated a liposome-microbubble delivery system as a vascular hydrophilic agonist carrier. Phenylephrine (Phe) or acetylcholine (Ach)-loaded liposomes were conjugated to microbubbles. The drug release was triggered by ultrasound (US), and the vascular response was assessed in rat aortic rings using an isolated organ chamber. Aortic rings incubated with Phe-liposome-microbubble conjugate, exposed to US showed a marked contractile response (0.79 ± 0.04 g) compared to empty liposomes conjugated to microbubbles, aortic rings exposed only to US, and Phe-liposome-microbubble conjugate without US exposure that elicited a minimal or no response. Expressed as %, contractile responses were 85.24 ± 4.31% and 12.62 ± 3.23% for Phe-Chol-liposome-microbubble conjugate and empty Chol-liposome-microbubble conjugate exposed to US, respectively. Addition of 1 × 10–5 M Ach to pre-contracted aortic rings decreased the contraction response from 1 to 0.21 g. The addition of Ach-liposome conjugate and exposure to US decreased the contraction response to 0.32 g. Additionally, the ED50 values for Phe and Ach released by US from liposome-microbubble conjugates were 3.6 × 10–8 M ± 2.8 × 10–9 M for Phe and 2.0 × 10−8 M ± 1.8 × 10–9 M. In conclusion, we evaluated a hybrid delivery system that consisted of loaded liposomes conjugated to microbubbles to deliver and release vascular agonists using UMMD. Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)1175-1186
Number of pages12
JournalDrug Delivery and Translational Research
Volume12
Issue number5
DOIs
Publication statusPublished - May 2022

Bibliographical note

Funding Information:
This work was supported by the Mexican Council for Science and Technology (CONACyT, grant number 1180 to BAE). J. Ángel Navarro-Becerra and Carlos A. Franco-Urquijo are fellows from CONACyT.

Publisher Copyright:
© 2021, Controlled Release Society.

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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