Reconsideration of drug release from temperature-sensitive liposomes.
The liposomal phase transition temperature was monitored in unstirred suspensions using a differential scanning calorimeter. The main and pre-transition temperatures under conditions of stirring were measured by the change in 90 degrees light scattering using a fluorescence spectrophotometer. Both methods show the same main transition temperature either with or without stirring. Temperature sensitive liposomes were made of DPPC (dipalmitoylphosphatidylcholine), DMPC (dimylisitoylphosphatidylcholine) or DSPC (distearoylphosphatidylcholine). The calcein release profile from the liposomes depends on the stirring time of the liposome suspension at the main transition temperature. For 1 h incubation, the leakage profile with and without stirring is similar. It had been hypothesized that temperature sensitive liposomes released drug at the main-transition temperature. However, calcein leakage from liposomes is observed also at the pre-transition temperature. Thus, a liposomal encapsulated drug will likely leak from DPPC liposomes at body temperature (37 degrees C), even if the liposomes were designed to have a higher main transition temperature.
Ono
Atsuo
A
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani Toyama, Japan. atsuo@ms.toyama-mpu.ac.jp
Takeuchi
Kentaro
K
Sukenari
Akemi
A
Suzuki
Tomoaki
T
Adachi
Isao
I
Ueno
Masaharu
M
D002152:Calorimetry, Differential Scanning; D004339:Drug Compounding; D005079:Excipients; D005452:Fluoresceins / Q000008:administration & dosage / Q000737:chemistry; D008027:Light; D008081:Liposomes / Q000737:chemistry*; D009391:Nephelometry and Turbidimetry; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence; D013696:Temperature
D005079:Excipients; D005452:Fluoresceins; D008081:Liposomes; D004364:Pharmaceutical Preparations; C007740:fluorexon