Temperature-dependent interaction of thermo-sensitive polymer-modified liposomes with CV1 cells

Egg yolk phosphatidylcholine liposomes modified with a copolymer of N-acryloylpyrrolidine and N-isopropylacrylamide having a lower critical solution temperature at ca. 40°C were prepared and an effect of temperature on their interaction with CV1 cells was investigated. The unmodified liposomes were taken up by the cells approximately to the same extent after 3 h incubation at 37 and 42°C. In contrast, uptake of the polymer-modified liposomes by CV1 cells decreased slightly at 37°C but increased greatly at 42°C, compared to the unmodified liposomes. Proliferation of the cells was partly prohibited by the incubation with the unmodified liposomes encapsulating methotrexate at 37 and 42°C. The treatment with the polymer-modified liposomes containing methotrexate at 37°C hardly effected the cell growth. However, the treatment at 42°C inhibited the cell growth completely. It is considered that the highly hydrated polymer chains attached to the liposome surface suppressed the liposome-cell interaction below the lower critical solution temperature of the polymer but the dehydrated polymer chains enhanced the interaction above this temperature. Because interaction of the polymer-modified liposomes with cells can be controlled by the ambient temperature, these liposomes may have potential usefulness as efficient site-specific drug delivery systems.