Gas-filled microbubbles (MB) are routinely used in the
clinic as
ultrasound contrast agents. MB are also increasingly explored as drug
delivery vehicles based on their ultrasound stimuli-responsiveness
and well-established shell functionalization routes. Broadening the
range of MB properties can enhance their performance in both imaging
and drug delivery applications. This can be promoted by systematically
varying the reagents used in the synthesis of MB, which in the case
of polymeric MB include surfactants. We therefore set out to study
the effect of key surfactant characteristics, such as the chemical
structure, molecular weight, and hydrophilic–lipophilic balance
on the formation of poly(butyl cyanoacrylate) (PBCA) MB, as well as
on their properties, including shell thickness, drug loading capacity,
ultrasound contrast, and acoustic stability. Two different surfactant
families (i.e., Triton X and Tween) were employed,
which show opposite molecular weight vs hydrophilic–lipophilic
balance trends. For both surfactant types, we found that the shell
thickness of PBCA MB increased with higher-molecular-weight surfactants
and that the resulting MB with thicker shells showed higher drug loading
capacities and acoustic stability. Furthermore, the higher proportion
of smaller polymer chains of the Triton X-based MB (as compared to
those of the Tween-based ones) resulted in lower polymer entanglement,
improving drug loading capacity and ultrasound contrast response.
These findings open up new avenues to fine-tune the shell properties
of polymer-based MB for enhanced ultrasound imaging and drug delivery
applications.