The Effects of Hydrophobically Modified Chitosan On Liposomes

We present results of work showing that chitosans that are hydrophobically modified with long alkyl groups have a protective influence on liposomes, allowing enhanced circulation times and sustained drug delivery. The alkyl groups partition into the lipid bilayers allowing the chitosan to form a coating that stabilizes the liposome. Such coated liposomes have extended circulation times and are protected from degradation by serum enzymes. We show the results of such coatings for spherical phospholipid  liposomes and for a class of novel tubular liposomes obtained through the addition of sphingolipids (ceramides) to the phospholipid bilayer. Details of liposome structure, dynamics, and morphology are characterized through cryoelectron microscopy and high resolution NMR. As the concentration of hydrophobically modified chitosan is increased, the system transitions from a liquid to a gel where the lipsomes act as nodes in a network structure. The transition is understood through detailed rheological characterization. Results are presented on drug release from such modified liposomes as correlated with liposome structure and system viscoelastic characteristics.