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

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

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