title: Laser-induced disruption of systemically administered liposomes for targeted drug delivery.
abstract: Liposomal formulations of drugs have been shown to enhance drug efficacy by prolonging circulation time, increasing local concentration and reducing off-target effects. Controlled release from these formulations would increase their utility, and hyperthermia has been explored as a stimulus for targeted delivery of encapsulated drugs. Use of lasers as a thermal source could provide improved control over the release of the drug from the liposomes with minimal collateral tissue damage. Appropriate methods for assessing local release after systemic delivery would aid in testing and development of better formulations. We use in vivo bioluminescence imaging to investigate the spatiotemporal distribution of luciferin, used as a model small molecule, and demonstrate laser-induced release from liposomes in animal models after systemic delivery. These liposomes were tested for luciferin release between 37 and 45 degrees C in PBS and serum using bioluminescence measurements. In vivo studies were performed on transgenic reporter mice that express luciferase constitutively throughout the body, thus providing a noninvasive readout for controlled release following systemic delivery. An Nd:YLF laser was used (527 nm) to heat tissues and induce rupture of the intravenously delivered liposomes in target tissues. These data demonstrate laser-mediated control of small molecule delivery using thermally sensitive liposomal formulations.
authors.affiliation: Stanford Medical Center, Department of Pediatrics, E-150 Clark Center, 318 Campus Drive, Stanford, California 94305, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mackanos
authors.forename: Malika
authors.initials: M
authors.lastname: Larabi
authors.forename: Rajesh
authors.initials: R
authors.lastname: Shinde
authors.forename: Dmitrii M
authors.initials: DM
authors.lastname: Simanovskii
authors.forename: Samira
authors.initials: S
authors.lastname: Guccione
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Contag
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000528:radiation effects*; D004339:Drug Compounding / Q000379:methods*; D007834:Lasers; D008081:Liposomes / Q000737:chemistry* / Q000528:radiation effects*; D008422:Materials Testing
chemical_list: D003692:Delayed-Action Preparations; D008081:Liposomes