Popping droplets for drug delivery

Vaporizable double emulsions, characterized by a central aqueous core, have demonstrated effectiveness in encapsulating hydrophilic drugs. This study aims to investigate the potential of incorporating an additional oil-layer in the double emulsions to encapsulate hydrophobic drugs. Vaporizable multi-layered emulsions were produced in three steps using perfluoropentane (PFP), phosphate-buffered saline (PBS), and sunflower oil. Curcumin, a natural anti-inflammatory drug, was dispersed in the oil phase. Krytox, polyglycerol polyricinoleate, and bovine serum albumin (BSA) were used as surfactants. PFP was sonicated in PBS (1:6) for 1 minute to create emulsion-1. Subsequently, emulsion-1 (1:4) was homogenized in oil to make emulsion-2. Emulsion-2 was homogenized in BSA (1:4) to yield emulsion-3 at 8000 rpm for 30 seconds. The vaporization pressure threshold was determined using 2 MHz focused ultrasound with a single-element transducer (f/# of 1.27, 0.5% duty cycle). B-mode imaging was conducted using a Verasonics Vantage 128 system with an L11-5v array to determine the droplet vaporization threshold, which was found to be 6.7 MPa. Curcumin-loading (0.87±0.1 mg) was significantly higher in the multi-layered emulsions than in single-layered BSA-shelled microbubbles (0.019±0.004 mg) (p<0.00001), indicating that multi-layered emulsions exhibit higher drug loading capacity.