Liposomes coated with hydrophobically modified hydroxyethyl cellulose: Influence of hydrophobic chain length and degree of modification

Abstract

Nanoparticulate systems with an uncharged hydrophilic surface may have a great potential in mucosal drug delivery. In the present study liposomes were coated with hydrophobically modified hydroxyethyl cellulose (HM-HEC) to create a sterically stabilized liposomal system with an uncharged surface. The aim was to clarify the influence of the amount of hydrophobic modification of HEC and the length of the hydrophobic moiety, on the stability of the system and on the release properties. HM-HEC with different degrees of hydrophobic modification (1 and 2 mol%) and hydrophobic groups with different chain lengths (C8, C12, C16) were included in the study, as well as fluid phase and gel phase liposomes. Both types of liposomes were successfully coated with HM-HEC containing 1 mol% of hydrophobic groups, while 2 mol% did not work for the intended pharmaceutical applications. The polymer coated gel phase liposomes were stable (size, zeta potential, leakage) for 24 weeks at 4 °C, with no differences between the C8 and C16 HM-HEC coating. For the fluid phase liposomes a size increase was observed after 24 weeks at 4 °C for all formulations; the C8 HM-HEC coated liposomes increased the most. No differences in the leakage during storage at 4 °C or in the release at 35 °C were observed between the fluid phase formulations. To conclude; HM-HEC with a shorter hydrophobic chain length resulted in a less stable product for the fluid phase liposomes, while no influence of the chain length was observed for the gel phase liposomes (1 mol% HM).