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

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 2mol%) 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 1mol% of hydrophobic groups, while 2mol% 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 (1mol% HM).

Studies on surface coating of phospholipid vesicles with a non-ionic polymer.

Liposomes coated with polymers may have a great potential in drug delivery. In this study, adsorption of the non-ionic hydroxyethyl cellulose (HEC) onto non-charged phospholipid vesicles was investigated. Both unmodified and hydrophobically modified (HM) HEC were included in the study. Possible interactions between the liposomes and the polymers were determined by changes in the size and the size distribution. Rheo-SALS measurements were carried out to verify the successfulness of the coating process. The stability was investigated by zeta potential measurements, UV-analysis and HPTLC. Mixing unmodified HEC (Mw 90,000 and 300,000) with the liposomes yielded no increase in the particle size. HM-HEC, however, was adsorbed onto both the fluid phase egg-PC liposomes and the gel phase DPPC liposomes. The Rheo-SALS measurements confirmed the successful coating of the liposomes. Complete coating resulted in increased chemical stability of the dispersion and in addition prevented aggregation. This study has shown that the non-ionic HM-HEC can be used to form polymer coated liposomes with neutral surface charge for enhanced stability.