title: Thermosensitive liposomal drug delivery systems: state of the art review.
abstract: Thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local hyperthermia or high intensity focused ultrasound. In vivo results have demonstrated strong evidence that external targeting is superior over passive targeting achieved by highly stable long-circulating drug formulations like PEGylated liposomal doxorubicin. Up to March 2014, the Web of Science listed 371 original papers in this field, with 45 in 2013 alone. Several formulations have been developed since 1978, with lysolipid-containing, low temperature-sensitive liposomes currently under clinical investigation. This review summarizes the historical development and effects of particular phospholipids and surfactants on the biophysical properties and in vivo efficacy of thermosensitive liposome formulations. Further, treatment strategies for solid tumors are discussed. Here we focus on temperature-triggered intravascular and interstitial drug release. Drug delivery guided by magnetic resonance imaging further adds the possibility of performing online monitoring of a heating focus to calculate locally released drug concentrations and to externally control drug release by steering the heating volume and power. The combination of external targeting with thermosensitive liposomes and magnetic resonance-guided drug delivery will be the unique characteristic of this nanotechnology approach in medicine.
authors.affiliation: Department of Internal Medicine III, University Hospital Munich, Germany ; Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Munich, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kneidl
authors.affiliation: Institute for Clinical Radiology, University Hospital Munich, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Peller
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Munich, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Winter
authors.affiliation: Department of Internal Medicine III, University Hospital Munich, Germany.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lindner
authors.affiliation: Department of Internal Medicine III, University Hospital Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hossann
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D050997:Nanomedicine / Q000379:methods*; D013696:Temperature
chemical_list: D008081:Liposomes
keywords: drug delivery; drug targeting; high intensity focused ultrasound; hyperthermia; phosphatidyloligoglycerol; thermosensitive liposomes