Temperature-dependent internal content release from liposomes was examined
using di-oleoylphosphatidylcholine (DOPC)/cholesterol liposomes with encaps
ulated Pluronic F127 molecules. The interaction of Pluronic F127 with the l
ipid bilayer at elevated temperature causes the release of encapsulated con
tents. Content release was measured using fluorescent markers of two differ
ent sizes: small, carboxyfluorescein (CF), and large, bovine serum albumin-
conjugated fluorescein iso-thiocyanate (BSA-FITC). Release of CF was studie
d using fluorescence de-quenching, while that of BSA-FITC was studied using
fluorescence emission quenching due to fluorescence resonance energy trans
fer (FRET). Temperature-controlled complete internal content release was ac
hieved at a precise temperature by controlling the concentration of the enc
apsulated Pluronic. Increasing cholesterol % in the liposome composition re
sulted in a sharper transition with temperature in content release. The ons
et temperature of content release increased with decrease in Pluronic conce
ntration. For the same Pluronic concentration, the onset temperature also d
epended on the size of the encapsulated marker and was higher for larger ma
rkers. We have established that onset of content release is determined by t
he critical micellar temperature (CMT) of the Pluronic. Temperature-sensiti
ve liposomes, made stealth using di-stearoyl(polyethylene glycol 5000) phos
phatidylethanolamine (DSPEG5000PE) in conjunction with Pluronic F127, had s
imilar temperature sensitivity and efficiency in content release compared t
o the non-stealth liposomes. (C) 2001 Published by Elsevier Science B.V.