Investigation of Liposome Cross-linked Hydrophobic Hydroxypropyl Methylcellulose Gels for Film Formation

We report that when liposomes are added to a solution of a hydrophobic water-soluble polymer, i.e., hydrophobically-modified hydroxypropyl methylcellulose (HM-HPMC), a liposome cross-linked gel (LCG) is formed due to the anchoring effect of the hydrophobic groups. In this study, we investigated LCG films made of HM-HPMC cross-linked with liposomes and evaluated the internal structure and drug release properties of the resulting films. The investigation of the LCG films indicated that only LCG formulations consisting of liposomes, HM-HPMC, and either 5% or 10% glycerol (GL) were capable of forming films with moderate strength and flexibility. These results suggested that both the three-dimensional network structure of LCG and the plasticizing effect of GL are necessary for film formulation. Structural evaluations of the resulting films were performed by small-angle X-ray scattering measurements and electron microscopy observations. These analyses revealed many structures presumably derived from liposomes in the film formulations, suggesting that the liposome structure is preserved in LCG films. The evaluation of drug release properties of the resulting films was performed by calculating drug release rates from film formulations containing 1% calcein (CAL, Mw 622.53) and fluorescently labeled dextran (FD4, Mw 4,000; FD40, Mw 40,000) as model drugs. The drug release rates from the film formulations containing CAL, FD4 and FD40 were in the order of CAL ≈ FD4 > FD40. The higher molecular weight of the drug may make the drug more difficult to diffuse through the film formulation due to the three-dimensional network structure of the LCG. These results indicated LCG can form film formulations containing water-soluble polymeric drugs with moderate strength and flexibility.