Temperature-sensitive release of adriamycin, an amphiphilic antitumor agent, from dipalmitoylphosphatidylcholine-cholesterol liposomes.
Drugs for temperature-sensitive liposomes have been limited to the hydrophilic drugs, such as methotrexate and cis-dichlorodiammineplatinum, with a low affinity for the lipid bilayer. It was, however, of importance to investigate whether the concept of temperature-sensitive liposomes can be extended to amphiphilic or lipophilic compounds, because some useful drugs are amphiphilic or lipophilic. In this study we tried to use adriamycin, an amphiphilic antitumor agent, as a drug for temperature-sensitive liposomes. In the absence of serum, the liposomes prepared from dipalmitoylphosphatidylcholine released adriamycin in a temperature-sensitive manner, i.e., they retained the major portion of entrapped adriamycin at a lower temperature 32 degrees C, and released around 70% of the drug at 42 degrees C, a temperature higher than the phase-transition temperature of the phospholipid. However, when serum was present, the liposomes were leaky even at 32 degrees C. To raise the stability of the liposomes, we included various mol% of cholesterol in the liposomal membrane and examined temperature sensitivity and stability of the liposomes in the presence of serum. Our results indicated that the liposomes including 20 mol% cholesterol were considerably stable and exhibited the maximal temperature-sensitive release of adriamycin in the presence of serum.
Tomita
T
T
Institute of Medical Science, University of Tokyo, Japan.
Watanabe
M
M
Takahashi
T
T
Kumai
K
K
Tadakuma
T
T
Yasuda
T
T
D015060:1,2-Dipalmitoylphosphatidylcholine; D002152:Calorimetry, Differential Scanning; D002784:Cholesterol; D004317:Doxorubicin / Q000008:administration & dosage / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism*; D013696:Temperature
D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; D004317:Doxorubicin; D002784:Cholesterol