title: Therapeutic applications of lipid-coated microbubbles.
abstract: Lipid-coated microbubbles represent a new class of agents with both diagnostic and therapeutic applications. Microbubbles have low density. Stabilization of microbubbles by lipid coatings creates low-density particles with unusual properties for diagnostic imaging and drug delivery. Perfluorocarbon (PFC) gases entrapped within lipid coatings make microbubbles that are sufficiently stable for circulation in the vasculature as blood pool agents. Microbubbles can be cavitated with ultrasound energy for site-specific local delivery of bioactive materials and for treatment of vascular thrombosis. The blood-brain barrier (BBB) can be reversibly opened without damaging the neurons using ultrasound applied across the intact skull to cavitate microbubbles within the cerebral microvasculature for delivery of both low and high molecular weight therapeutic compounds to the brain. The first lipid-coated PFC microbubble product is currently marketed for diagnostic ultrasound imaging. Clinical trials are currently in process for treatment of vascular thrombosis with ultrasound and lipid-coated PFC microbubbles (SonoLysis Therapy). Targeted microbubbles and acoustically active PFC nanoemulsions with specific ligands can be developed for detecting disease at the molecular level and targeted drug and gene delivery. Bioactive compounds can be incorporated into these carriers for site-specific delivery. Our aim is to cover the therapeutic applications of lipid-coated microbubbles and PFC emulsions in this review.
authors.affiliation: ImaRx Therapeutics, Inc., Tuscon, Arizona, USA. eunger@imarx.com
authors.forename: Evan C
authors.initials: EC
authors.lastname: Unger
authors.forename: Thomas
authors.initials: T
authors.lastname: Porter
authors.forename: William
authors.initials: W
authors.lastname: Culp
authors.forename: Rachel
authors.initials: R
authors.lastname: Labell
authors.forename: Terry
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Reena
authors.initials: R
authors.lastname: Zutshi
mesh_terms: D001812:Blood-Brain Barrier; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D005466:Fluorocarbons; D018014:Gene Transfer Techniques; D006801:Humans; D008055:Lipids; D008863:Microspheres; D010100:Oxygen / Q000008:administration & dosage; D015912:Thrombolytic Therapy / Q000379:methods; D014465:Ultrasonics; D014463:Ultrasonography / Q000379:methods
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D005466:Fluorocarbons; D008055:Lipids; D010100:Oxygen