title: Focused ultrasound mediated drug delivery from  temperature-sensitive liposomes: in-vitro  characterization and validation.
abstract: Nanomedicine-based delivery with non-invasive techniques is a promising approach to increase local drug concentration and to reduce systemic side effects. Focused ultrasound (FUS) has become a promising strategy for non-invasive local drug delivery by mild hyperthermia. In this study, traditional temperature-sensitive liposomes (TTSLs) encapsulating doxorubicin (DOX) were evaluated for FUS-mediated drug delivery with an in-vitro FUS setup. In-vitro studies showed quantitative release of the DOX from the lumen of the temperature-sensitive liposomes when heated to 42 °C with FUS using 1 MHz sinusoidal waves at 1.75 MPa for 10 min. No release was observed when heated at 37 °C. Moreover, we showed that DOX released from TTSLs by FUS is as efficiently internalized by glioblastoma cells as free DOX at 37 °C. In-vitro therapeutic evaluation showed that exposure of a cell monolayer to FUS-activated TTSLs induced a 60% and a 50% decrease in cell viability compared to cell medium and to TTSLs preheated at 37 °C, respectively. Using an in-vitro 3D cell culture model, the results showed that after FUS-mediated hyperthermia, preheated liposomes induced a 1.7-fold decrease in U-87 MG spheroid growth in comparison to the preheated liposomes at 37 °C. In conclusion, our results show that in-vitro FUS allows the evaluation of TTSLs and does not modify the cellular uptake of the released DOX nor its cytotoxic activity.
authors.forename: J-M
authors.initials: JM
authors.lastname: Escoffre
authors.forename: A
authors.initials: A
authors.lastname: Novell
authors.forename: M
authors.initials: M
authors.lastname: de Smet
authors.forename: A
authors.initials: A
authors.lastname: Bouakaz
mesh_terms: D001692:Biological Transport; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D008081:Liposomes; D015203:Reproducibility of Results; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology; D013696:Temperature; D014465:Ultrasonics
chemical_list: D008081:Liposomes; D004317:Doxorubicin