Enhancement of the Phase Transition Permeability of DPPC Liposomes by Incorporation of MPPC: A New Temperature-Sensitive Liposome for use with Mild Hyperthermia

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Abstract
The present study describes a novel method of preparing thermosensitive liposomes by compositional modification, incorporating a highly bilayer compatible lysolipid, 1 -Palmitoyl-2-Hydroxy-sn-Glycero-3-Phosphocholine (MPPC) into the gel phase liposomes composed of l,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC). This compositional modification of the liposomes achieved a significantly enhanced release of entrapped liposome contents at mild hyperthermic temperatures between 39°C-40°C as compared to pure DPPC which released only 20% of contents over a broader range of 40°C-45°C, and the more conventional (DPPC/DSPC-based) temperature-sensitive liposomes that released more slowly in the 43°C-45°C range. Also, the temperature range over which the maximum release occurred for the DPPC:MPPC system remained very narrow and maximum release is achieved after only a tens of seconds of heating. Characterization of the liposome formulation was carried out by studying the release profiles of entrapped carboxy-fluorescein from the liposomes at various temperatures and time intervals. The cumulative release profiles of the formulation were correlated with differential scanning calorimetric scans of the same compositions in order to understand the molecular mechanisms associated with the release of entrapped marker. The stability and thermal sensitivity of the liposomes in the presence of phosphate buffered saline and human serum albumin were evaluated. The new concept for triggered release presented here is that upon raising the temperature of the gel phase liposome to 39°C-°C, the desorption of MPPC from liquid phase regions as the first lipid begins to melt creates enhanced defect formation which dramaticaly increases the permeability of the memrbane to the entrapped CF.