Novel Temperature-Sensitive Liposomes with Prolonged Circulation Time

摘要: Hyperthermia increases the efficiency of various chemotherapeutic drugs and is administered as an adjunct to chemotherapy for treatment cancer patients. The temperature-dependent effect can be strongly increased by use temperature-sensitive liposomes in combination with regional hyperthermia, which specifically releases entrapped drug heated tumor tissue. novel lipid 1.2-dipalmitoyl- sn -glycero-3-phosphoglyceroglycerol (DPPGOG), closely related naturally occurring -glycero-3-phosphoglycerol, -glycero-3-phosphocholine 1.2-distearoyl- provides long-circulating favorable properties under mildly hyperthermic conditions (41–42°C). DPPGOG facilitates temperature-triggered release from these (diameter, 175 nm) leads a substantially prolonged plasma half-life encapsulated t 1/2 = 9.6 h hamsters 5.0 rats. Quantitative fluorescence microscopy amelanotic melanoma grown transparent dorsal skin fold chamber demonstrated accumulation tissue after i.v. application (42°C 1 h). mean area curve concentration was more than sixfold new compared nonliposomal delivery. In summary, we present DPPGOG-based liposomal formulation enabling long circulation time combined fast efficient mild hyperthermia. This adds positively results lipid-grafted polyethylenglycol used thus far temperaturesensitive widens possibilities clinical applications.