Dissolution Behavior of Lipid Monolayer-Coated, Air-Filled Microbubbles: Effect of Lipid Hydrophobic Chain Length

The gas transport properties and dissolution behavior of the lipid monolayer shell coating a micron-scale bubble (microbubble) are of particular interest for developing stable ultrasound contrast agents, drug delivery vehicles, and efficient oxygen carriers. In the current study, Epstein and Plesset's model for the dissolution of a bubble into a quiescent, degassed medium was modified to include a term for the gas permeation resistance of the lipid shell. The shell resistances for a homologous series of phospholipids were determined by comparing this model to experimental data of lipid-coated, air-filled microbubbles dissolving in a degassed aqueous medium. The gas permeation resistance is a significant factor in controlling the dissolution rate of lipid-coated microbubbles and was found to increase monotonically with lipid hydrophobic chain length. During the dissolution process, lipid was shed from the shell in a continuous manner for short-chain lipids to accommodate the shrinking volume of the gas core. A cyclic process of buckling and lipid shedding was observed for long-chain lipids and a mechanism involving adhesive zippering of apposing monolayers is proposed to describe this phenomenon.