Hydrophobically-modified copolymers of
N-isopropylacrylamide bearing a pH-sensitive moiety were investigated for the preparation of pH-responsive
liposomes and polymeric
micelles. The copolymers having the hydrophobic anchor randomly distributed within the polymeric chain were found to more efficiently destabilize egg
phosphatidylcholine (
EPC)/
cholesterol liposomes than the alkyl terminated
polymers. Release of both a highly-water soluble fluorescent contents marker,
pyranine, and an amphipathic cytotoxic anti-
cancer drug,
doxorubicin, from copolymer-modified
liposomes was shown to be dependent on pH, the concentration of copolymer, the presence of other
polymers such as
polyethylene glycol, and the method of preparation. Both
polymers were able to partially stabilize
EPC liposomes in human serum. These
polymers were found to self-assemble to form
micelles. The critical association concentration was low (9--34 mg/l) and influenced by the position of the alkyl chains. In
phosphate buffered saline, the
micelles had a bimodal size distribution with the predominant population having a mean diameter of 35 nm. The polymeric
micelles were studied as a delivery system for the
photosensitizer aluminum chloride phthalocyanine, (AlClPc), currently evaluated in
photodynamic therapy. pH-Responsive polymeric
micelles loaded with AlClPc were found to exhibit increased cytotoxicity against EMT-6 mouse mammary cells in vitro than the control
Cremophor EL formulation.