Thermosensitive liposomal drug delivery systems: state of the art review

Barbara Kneidl,1,2 Michael Peller,3 Gerhard Winter,2 Lars H Lindner,1 Martin Hossann11Department of Internal Medicine III, University Hospital Munich, 2Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, 3Institute for Clinical Radiology, University Hospital Munich, Ludwig-Maximilians University, Munich, GermanyAbstract: 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.Keywords: thermosensitive liposomes, phosphatidyloligoglycerol, hyperthermia, high intensity focused ultrasound, drug delivery, drug targetin

Liposomes for Hyperthermia Triggered Drug Release

The use of thermosensitive liposomes (TSLs) for anticancer treatment that were first described in the seventies has gained an increasing amount of attention over the years. In recent decades, various TSL formulations have been designed and tested in many different ways, all having various advantages and disadvantages. We here give an overview on the parameters: (1) base lipids; (2) cholesterol; (3) surface modification; (4) release improvement; (5) encapsulated drugs; (6) active targeting and (7) testing procedures of this broad variety of TSLs. By these means, we aim to establish a broader understanding on how to adequately design a TSL and to test these in a reliable manner. Furthermore, we provide a critical view on the investigated aspects of TSL that were successful and unsuccessful and highlight which areas still require more follow up research.</jats:p

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TIB Hannover: RN 5905(2196) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman