Hydrophilic Cargo-Loaded Microbubbles for Ultrasound-Triggered Local Delivery
Year: 2020
Type: dissertation
Abstract: Microbubbles are intravenous ultrasound-responsive agents that can cavitate upon insonation. There is ongoing interest in incorporating hydrophilic therapeutic and imaging agents into microbubbles for local, ultrasound-triggered delivery. A proof-of-concept microbubble capable of carrying hydrophilic molecules, providing ultrasound contrast, and cavitating was designed. Calcein was selected as a model cargo for optical verification of co-localization. First, 75% v/v Span 80 and 25% v/v Tween 80 surfactants were selected to solubilize calcein in cyclooctane. Second, calcein-loaded oil was emulsified as microdroplets stabilized with 2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-5000] phospholipids. Microdroplets were lyophilized, decafluorobutane gas-filled, and saline reconstituted to form calcein-loaded microbubbles. These were characterized for size distribution, calcein loading, contrast enhancement and cavitation. Calcein-loaded microbubbles (peak: 4.3 μm) demonstrated cargo co-localization and a concentration per microbubble volume of 0.077±0.038 mg/mL. Microbubbles provided ultrasound contrast and underwent inertial cavitation at MI≥0.77. This synthesis method may be extended to encapsulate other hydrophilic cargo in acoustically-active carriers.
Source: TSpace (University of Toronto)
Author: Samantha Chow
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W3183439244