Preparation and Evaluation of Temperature Sensitive Liposomes Containing Adriamycin and Cytarabine

Temperature sensitive liposomes(TSL) containing adriamycin (ADM) and cytarabine (Ara-C) were prepared. ADM and Ara-C were selected as model compounds of amphiphilic and hydrophilic drug, respectively. Encapsulation efficiency of ADM entrapped into TSL was about twice greater than that of Ara-C. It might be due to different polarity of the drug, Lipid compositions of TSL had no effect on the encapsulation efficiency of drugs. Thermal behavior of TSL using a differential scanning calorimetry (DSC) was also investigated. Phase transition of TSL using a differential scanning calorimetry (DSC) was also investigated. Phase transition temperature $(T_c)$ of TSL was dependent on the lipid compositions of TSL ADM broadened thermogram of TSL but Ara-C did not. However, $T_c$ of TSL was not changed by any drug. Release rate of drugs was highly dependent on temperature. The release profile of ADM was similar to that of Ara-C. The maximum release rate of drugs from TSL was occurred at the near $T_c$ and observed at $39-41^\circ{C}$ for DPPC (Dipalmitoylphosphatidylcholine) only, $52-54^\circ{C}$ for DPPC and DSPC (1:1), respectively. Effect of human serum alburmin (HAA) on the release rate of ADM was investigated. HSA had no significant effect on the release of ADM below $T_c$. However, ADM release from TSL was increased at the near and above $T_c$. The HSA-induced leakage of drug may result from the interaction of liposomal constituents with HSA structure at the near TEX>$4^\circ{C}$. From the fact that the release profiles of ADM from freshly prepared TSL and stored TSL for 1 week at TEX>$4^\circ{C}$ was not changed, the TSL was considered to be stable for at least 1 week at TEX>$4^\circ{C}$. Based on these findings, TSL may be useful to deliver drugs to preheated target sites due to its thermal behaviors.