Shell effects on acoustic performance of a drug-delivery system activated by ultrasound

The composition of microcapsules designed for drug delivery significantly impacts their properties. Ultrasound contrast agents, consisting of stabilized microbubbles (MBs), have emerged as versatile potential drug delivery vehicles to both image and overcome challenges associated with systemic chemotherapy. In our development of polylactic acid MBs decorated with immune-shielding polyethylene glycol chains, we have shown that the balance between acoustic behavior and immune avoidance was scalable and amenable to two distinct PEGylation methods, either incorporation of 5 wt% PEGylated PLA or insertion of 1 wt% PEGylated lipid (LipidPEG) in the polymeric shell. Here we describe the effects of shell compositions on MB functionalization for use in targeted cancer therapy. We chose tumor necrosis factor-related apoptosis inducing ligand (TRAIL) as the targeting ligand, motivated by the ability to both target cells and selectively induce tumor cell death upon binding. Additionally, the MBs were designed to co-encapsulate the chemotherapeutic doxorubicin (Dox) within the shell that works with TRAIL to sensitize resistant cells. We have previously shown that the MBs shatter in response to ultrasound focused at the tumor site, delivering drug-eluting fragments. This study demonstrates the effect of shell characteristics and MB functionalization (TRAIL-ligated and Dox-loaded MBs) on the acoustic response of MBs, and the cumulative effect of shell type. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3189-3196, 2017.