Tailor-Made Single-Core PLGA Microbubbles as Acoustic Cavitation Enhancers for Therapeutic Applications

Abstract

Microbubbles (MBs), being gas bubbles encapsulated inside a solid shell, have been investigated extensively in the field of therapeutic ultrasound as acoustic cavitation enhancers. Hard-shell MBs have an advantage over soft-shell MBs due to their improved stability. Poly­(lactic-co-glycolic acid) (PLGA) is one of the most attractive polymers for hard-shell MB synthesis; however, very little is known regarding the effect of synthesis parameters on the acoustic cavitation activity of PLGA MBs and the tunability of this activity. In this study, by manipulating the synthesis parameters, we were able to control the characteristics of the MBs, such as their internal structure, gas core, size distribution, and shell thickness, which significantly affect the total acoustic cavitation activity that they exhibit (i.e., their cavitation dose). We showed that single-core MBs filled with C3F8 gas can produce cavitation effects for extended periods under continuous circulation. These MBs exhibited high stability, and their cavitation activity was not affected by prior circulation in the system. Preliminary in vivo results demonstrated that intravenously injected MBs did not cause adverse effects and produced cavitation activity that increased the permeability of the pig blood–brain barrier. Although more tests should be performed to evaluate the MB long-term safety and activity in vivo, these encouraging results suggest that our PLGA MBs have potential for future therapeutic applications as cavitation enhancers.

Three birds with one stone: co-encapsulation of diclofenac and DL-menthol for realizing enhanced energy deposition, glycolysis inhibition and anti-inflammation in HIFU surgery

“…The treatment settings was shown in Additional file 1: Figure S9. Without HIFU irradiation, negligible tumor inhibition effect could be found in the group treated with DLM@PLGA NPs, indicating the good biocompatibility of PLGA-based nanocarriers as previously reported [44,45]. As shown in Additional file 1: Figure S10, an in vivo imaging system (IVIS) was further used to examine the distribution of fluorescent Cy5.5@PLGA NPs (which was used as a fluorescent substitution of PLGA-based NPs in this study) in tumor-bearing mice.…”

Barrier-breaking effects of ultrasonic cavitation for drug delivery and biomarker release

“…To improve the in vivo persistence of microbubbles, Chen et al incorporated poly (lactic-co-glycolic acid) (PLGA) polymer into the lipid shell of microbubbles [41] . Tsirkin et al further showed that the addition of PLGA produced hard shell microbubbles with high stability in circulation and an extended cavitation time (approximately 2-fold) [42] .…”

Ultrasound‐Responsive Aqueous Two‐Phase Microcapsules for On‐Demand Drug Release

“…The application of FUS primarily causes breakdown of the soft inner dextran phase while also causing some breakdown of the stiff outer PEGDA phase. Compared to microbubbles (which are typically several microns in diameter [2i, 5, 19] ), these biphasic microcapsules can carry large payloads and be used for pulsatile payload release over days. An overview of our process can be seen in Movie S1.…”