Phase transformation of a liposomal dispersion into a micellar solution induced by drug-loading

Loading a liposomal dispersion with drug may cause a phase transformation into a micellar solution. The present contribution presents a detailed physicochemical characterization and an overall model which describes transformation due to the properties of any drug.

Characterization of liposomal dispersions was obtained by photon correlation spectroscopy (PCS) and small angle X-ray scattering (SAXS). Microstructure of colloidal solutions was analysed by 31P-NMR and SAXS.

At weight ratios of phospholipid to drug from 16:1 to 2:1, liposomal dispersions of milky-white appearance and a mean particle size of about 200 nm were obtained. From a ratio of phospholipid to drug of 1:1 downwards, the systems became nearly transparent. The particle size decreased to a value below 25 nm. SAXS also revealed the change of the colloids. Down to a ratio of phospholipid to drug of 2:1 the systems were described as bilayer-structured. At and below the ratio of 1:1, a mixed micelle was indicated. In the 31P-NMR spectra, the transformation is emphasized by both appearance and disappearance of signals. A model based on the theory of self-assembly is presented which explains the phase transformation due to drug amphiphilicity.

We predict that the model presented will hold in general only due to the amphiphilic properties of the drug.