Shaping the synthesis of surfactant-stabilized oxygen microbubbles to accommodate encapsulated drug

Making waves: how ultrasound-targeted drug delivery is changing pharmaceutical approaches

“…87 Building upon this work, this group has also investigated loading lonidamine within these oxygen-carrying microbubbles to achieve multi-modal UTDD against hypoxic tumors, including breast and head and neck cancers. 88,89 Significant efforts have also been devoted to sonoporation of pancreatic ductal adenocarcinoma (PDAC), since this remains a lethal cancer with an overall five year survival rate of approximately 10% and a median survival for all patients of less than 6 months. 90,91 Standard-of-care chemotherapy regimens have only marginally increased overall survival rates, and thus, are largely ineffective in preventing recurrence and eventual death.…”

“…87 Building upon this work, this group has also investigated loading lonidamine within these oxygen-carrying microbubbles to achieve multi-modal UTDD against hypoxic tumors, including breast and head and neck cancers. 88,89…”

Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen

“…Unloaded microbubbles were prepared by a previously described method [34]. Briefly, micelles were formed by heating 1.288 g of TPGS dissolved in 25 mL of 37 • C phosphatebuffered saline (PBS) and placed on a stir plate for ~30 min.…”

“…In parallel, 1.464 g of sorbitan monostearate and 1.5 g of NaCl in 25 mL PBS solution were autoclaved (Yamato Scientific Co., Ltd., Tokyo, Japan) for 35 min at 125 • C to aid in dispersion. Initial micelle formation was found in a previous study to generate over double the microbubble yield [34]. The autoclaved solution was immediately added to the TPGS micelle solution and allowed to cool to room temperature under continuous mixing.…”

“…The second method (LP2) followed similar methods but combined drugs for incubation in TPGS micelles for 48 h before microbubble fabrication, thus first forming mixed-drug micelles. Following these two distinct methods, any drug interaction during the micellation step could be identified while preserving the advantages of entrapping the drug in TPGS micelles prior to the sonication step, a method that we have identified previously as producing a doubling of microbubble yields [34]. The entire process is outlined in Figure 2.…”