Targeted Microbubbles for Drug, Gene, and Cell Delivery in Therapy and Immunotherapy

Abstract

Microbubbles are 1–10 μm diameter gas-filled acoustically-active particles, typically stabilized by a phospholipid monolayer shell. Microbubbles can be engineered through bioconjugation of a ligand, drug and/or cell. Since their inception a few decades ago, several targeted microbubble (tMB) formulations have been developed as ultrasound imaging probes and ultrasound-responsive carriers to promote the local delivery and uptake of a wide variety of drugs, genes, and cells in different therapeutic applications. The aim of this review is to summarize the state-of-the-art of current tMB formulations and their ultrasound-targeted delivery applications. We provide an overview of different carriers used to increase drug loading capacity and different targeting strategies that can be used to enhance local delivery, potentiate therapeutic efficacy, and minimize side effects. Additionally, future directions are proposed to improve the tMB performance in diagnostic and therapeutic applications.

Influence of protein nativity on the stability of bovine serum albumin coated microbubbles

“…Reported values of BSA-coated microbubble shell thickness indicate ranges from 15 to 150 nm. 31 Based on this, and our experimental measurements (data not shown), we take the shell thickness to be ∼100 nm, for both NBSA and DBSA. In order to find the pore size and porosity, we estimate the values of d and ϵ from our computational void volume calculations.…”

Effect of Poly(ethylene glycol) Configuration on Microbubble Pharmacokinetics

“…The concentration and size distributions (number- and volume-weighted) of the MBs were measured using a Multisizer 3 Coulter Counter (Beckman Coulter). The MB gas volume fraction (φ MB ) was determined by integrating the area under the curve when plotting the MB concentration ( c , MBs/mL) against the MB volume (μL), as defined by eq 3: , φ MB = ∫ 0 ∞ c d v …”

“…Microbubbles (MBs) are 1–10 μm diameter gas-filled microspheres, typically comprising a perfluorocarbon gas core and a thin stabilizing shell of phospholipid, protein, or polymer. − Owing to their versatile acoustic behavior, MBs hold great promise for ultrasound imaging and therapy. − However, whether utilized in clinical or research practice, challenges persist in their formulations, characterized by limited in vivo circulation (usually 2–5 min) and variations in composition, size distribution, concentration, and recommended dosage. , These variations result in diverse acoustic responses, , biological effects, , and biomedical outcomes, − prompting the need to reveal interrelationships between MB composition and biointeractions while minimizing confounding effects of MB size distribution and dose. Such discoveries may inspire innovative approaches to extend MB circulation persistence, improve pharmacokinetics, establish standardized dosing, and enhance clinical utility.…”

Putting the sting back in STING therapy: novel delivery vehicles for improved STING activation

“…Originally used in the clinic as contrast agents for ultrasound (US) imaging, microbubbles (MBs) now show promise for drug delivery in clinically translatable immunotherapeutic applications (Ho et al, 2020;Navarro-Becerra and Borden, 2023). Comprised of a gas core and a lipid, protein, or polymer shell, these 1-10 µm particles are elastic and able to oscillate in an acoustic field (Tinkov et al, 2009).…”