Title:Microbubbles as a Vehicle for Gene and Drug Delivery: Current Clinical Implications and Future Perspectives
Volume: 18
Issue: 15
Author(s): Nicolas A Geis, Hugo A Katus and Raffi Bekeredjian
Affiliation:
Keywords:
Microbubble, UTMD, ultrasound, drug delivery, gene therapy, sonoporation, ultrasound contrast agent, triggered release
Abstract: Ultrasound targeted microbubble destruction (UTMD) has evolved as a novel system for non-invasive, organ- and tissuespecific
drug and gene delivery. Initially developed as ultrasound contrast agents, microbubbles (MBs) have increasingly gained attention
for their ability to directly deliver different classes of bioactive substances (e.g. genes, drugs, proteins, gene silencing constructs) to various
organ systems and tumors. Bioactive substances can be attached to or incorporated in the microbubble shells. Applying ultrasound at
their resonance frequency, microbubbles oscillate. When using higher ultrasound energies, oscillation amplitudes increase, finally resulting
in microbubble destruction. This leads to increased capillary and cell membrane permeability in the immediate vicinity of the ruptured
MBs, thus facilitating tissue and cell penetration of co-administered or loaded bioactive substances. Numerous proof of principle
studies have been performed, demonstrating the broad potential of UTMD as a site-specific, non-invasive therapeutic tool, delivering microbubble
payload to various target tissues and organ systems or facilitating uptake of bioactive substances into tissues or cells. This review
focuses on current in vivo studies and therapeutic approaches of UTMD. Promising results give hope for future clinical applications
of this novel non-viral vector system. Nevertheless, several limitations remain, which will also be discussed in this review article.
