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bioRxiv · 10.64898/2026.06.28.735147

Development and Characterization of Ultrasound-Activated Polymeric Microdroplets for Targeted Chemotherapy

Whiting, J. A.·Dara, A. Y. A. H.·Kwan, J. F.·Kubanek, J.
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Abstract

Potent antineoplastics, such as afatinib and freebase doxorubicin, are associated with systemic toxicity. To address this issue, we developed a carrier that releases drugs, including afatinib and doxorubicin, specifically at the focus of low-intensity ultrasound. This remotely triggered and focal approach enables the release of drugs specifically at the ultrasound focus, thus mitigating undesirable off-target effects, and at concentrations governed by the duration of the applied ultrasound. We produced ultrasound-sensitive microdroplets with high encapsulation efficiencies (39.6% for afatinib and 46.6% for doxorubicin). The microdroplets consist of an ultrasound-sensitive drug delivery system based on a methoxy poly(ethylene glycol)-poly(D, L-lactide) diblock copolymer (mPEG-PDLLA) and perfluorooctyl bromide (PFOB). Antineoplastic agents were encapsulated within these microdroplets via co-evaporation during particle synthesis. The microdroplets released doxorubicin and afatinib in an ultrasound-pressure-dependent manner, with fitted half-maximal release pressures (P50) of 0.61 MPa and 0.72 MPa, respectively. Together, the effective encapsulation of hydrophobic antineoplastic agents and the dose-dependent ultrasound-triggered release provide a new method for targeted drug delivery and a foundation for future targeted chemotherapies. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/735147v3_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@6454c1org.highwire.dtl.DTLVardef@f87630org.highwire.dtl.DTLVardef@174ce3org.highwire.dtl.DTLVardef@1b8dc91_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIWe developed an ultrasound-triggered drug release vehicle using biocompatible materials. C_LIO_LIThe vehicle has high encapsulation efficiency for hydrophobic chemotherapeutics. C_LIO_LIWe demonstrated dose-dependent release. C_LIO_LIThe vehicle provides a platform for targeted chemotherapy. C_LI

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Whiting, J. A., Dara, A. Y. A. H., Kwan, J. F., Kubanek, J.. 2026-06-29. Development and Characterization of Ultrasound-Activated Polymeric Microdroplets for Targeted Chemotherapy. https://doi.org/10.64898/2026.06.28.735147

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