title: A thermoresponsive bubble-generating liposomal system for triggering localized extracellular drug delivery.
abstract: The therapeutic effectiveness of chemotherapy is optimal only when tumor cells are subjected to a maximum drug exposure. To increase the intratumoral drug concentration and thus the efficacy of chemotherapy, a thermoresponsive bubble-generating liposomal system is proposed for triggering localized extracellular drug delivery. The key component of this liposomal formulation is the encapsulated ammonium bicarbonate (ABC), which is used to create the transmembrane gradient needed for a highly efficient encapsulation of doxorubicin (DOX). At an elevated temperature (42 °C), decomposition of ABC generates CO(2) bubbles, creating permeable defects in the lipid bilayer that rapidly release DOX and instantly increase the drug concentration locally. Because the generated CO(2) bubbles are hyperechogenic, they also enhance ultrasound imaging. Consequently, this new liposomal system encapsulated with ABC may also provide an ability to monitor a temperature-controlled drug delivery process.
authors.affiliation: Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.
authors.forename: Ko-Jie
authors.initials: KJ
authors.lastname: Chen
authors.forename: Hsiang-Fa
authors.initials: HF
authors.lastname: Liang
authors.forename: Hsin-Lung
authors.initials: HL
authors.lastname: Chen
authors.forename: Yucai
authors.initials: Y
authors.lastname: Wang
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Cheng
authors.forename: Hao-Li
authors.initials: HL
authors.lastname: Liu
authors.forename: Younan
authors.initials: Y
authors.lastname: Xia
authors.forename: Hsing-Wen
authors.initials: HW
authors.lastname: Sung
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004058:Diffusion; D004317:Doxorubicin / Q000737:chemistry*; D006358:Hot Temperature; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D045423:Microbubbles
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D008051:Lipid Bilayers; D008081:Liposomes; D004317:Doxorubicin