Abstract
Objective: Phase-change contrast agents (PCCAs) are perfluorocarbon nanodroplets (NDs)
that have been widely studied for ultrasound imaging in vitro, pre-clinical studies, and most recently incorporated a variant of PCCAs, namely
a microbubble-conjugated microdroplet emulsion, into the first clinical studies. Their
properties also make them attractive candidates for a variety of diagnostic and therapeutic
applications including drug-delivery, diagnosis and treatment of cancerous and inflammatory
diseases, as well as tumor-growth tracking. However, control over the thermal and
acoustic stability of PCCAs both in vivo and in vitro has remained a challenge for expanding the potential utility of these agents in novel
clinical applications. As such, our objective was to determine the stabilizing effects
of layer-by-layer assemblies and its effect on both thermal and acoustic stability.
Methods: We utilized layer-by-layer (LBL) assemblies to coat the outer PCCA membrane
and characterized layering by measuring zeta potential and particle size. Stability
studies were conducted by; 1) incubating the LBL-PCCAs at atmospheric pressure at
37C and 45C followed by; 2) ultrasound-mediated activation at 7.24 MHz and peak-negative pressures
ranging from 0.71 - 5.48 MPa to ascertain nanodroplet activation and resultant microbubble
persistence. The thermal and acoustic properties of decafluorobutane gas-condensed
nanodroplets (DFB-NDs) layered with 6 and 10 layers of charge-alternating biopolymers,
(LBLNDs and LBLNDs) respectively, were studied and compared to non-layered DFB-NDs. Half-life determinations
were conducted at both 37C and 45C with acoustic droplet vaporization (ADV) measurements occurring at 23C. Discussion: Successful application of up to 10 layers of alternating positive and
negatively charged biopolymers onto the surface membrane of DFB-NDs was demonstrated.
Two major claims were substantiated in this study; namely, (1) biopolymeric layering
of DFB-NDs imparts a thermal stability up to an extent; and, (2) both LBLNDs and LBLNDs did not appear to alter particle acoustic vaporization thresholds, suggesting
that the thermal stability of the particle may not necessarily be coupled with particle
acoustic vaporization thresholds. Conclusion: Results demonstrate that the layered
PCCAs had higher thermal stability, where the half-lifes of the LBLNDs are significantly increased after incubation at 37C and 45C. Furthermore, the acoustic vaporization profiles the DFB-NDs, LBLNDs, and LBLNDs show that there is no statistically significant difference between the acoustic
vaporization energy required to initiate acoustic droplet vaporization.
Keywords
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Article info
Publication history
Published online: February 14, 2023
Accepted:
December 8,
2022
Received in revised form:
December 7,
2022
Received:
April 4,
2022
Identification
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