title: Delivery of chlorambucil using an acoustically-triggered perfluoropentane emulsion.
abstract: Ultrasound-mediated delivery systems have mainly focused on microbubble contrast agents as carriers of drugs or genetic material. This study uses micron-sized, perfluoropentane (PFP) emulsions as carriers of chlorambucil (CHL), a lipophilic chemotherapeutic. The release of CHL is achieved via acoustic droplet vaporization (ADV), whereby the superheated emulsion is converted into gas bubbles using ultrasound. Emulsions were made using an albumin shell and soybean oil as the CHL carrier. The ratio of the PFP to soybean oil phases in the droplets and the fraction of droplets that vaporize per ultrasound exposure were shown to correlate with droplet diameter. A 60-min incubation with the CHL-loaded emulsion caused a 46.7% cellular growth inhibition, whereas incubation with the CHL-loaded emulsion that was exposed to ultrasound at 6.3 MHz caused an 84.3% growth inhibition. This difference was statistically significant (p < 0.01), signifying that ADV can be used as a method to substantially enhance drug delivery.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. mfabiill@umich.edu
authors.forename: Mario L
authors.initials: ML
authors.lastname: Fabiilli
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Haworth
authors.forename: Ian E
authors.initials: IE
authors.lastname: Sebastian
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Kripfgans
authors.forename: Paul L
authors.initials: PL
authors.lastname: Carson
authors.forename: J Brian
authors.initials: JB
authors.lastname: Fowlkes
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000737:chemistry; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects*; D002699:Chlorambucil / Q000008:administration & dosage* / Q000737:chemistry*; D006224:Cricetinae; D003412:Cricetulus; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions / Q000737:chemistry / Q000528:radiation effects; D005466:Fluorocarbons / Q000737:chemistry* / Q000528:radiation effects*; D013010:Sonication; D010420:Pentanes
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002699:Chlorambucil; D004655:Emulsions; D005466:Fluorocarbons; C008806:perfluoropentane; D010420:Pentanes