PHASE-TRANSFORMATION OF A LIPOSOMAL DISPERSION INTO A MICELLAR SOLUTION INDUCED BY DRUG-LOADING

Purpose. Loading a liposomal dispersion with drug may cause a phase tr ansformation into a micellar solution. The present contribution presen ts a detailed physicochemical characterization and an overall model wh ich describes transformation due to the properties of any drug. Method s. Characterization of liposomal dispersions was obtained by photon co rrelation spectroscopy (PCS) and small angle X-ray scattering (SAXS). Microstructure of colloidal solutions was analysed by P-31-NMR and SAX S. Results. At weight ratios of phospholipid to drug from 16:1 to 2:1, liposomal dispersions of milky-white appearance and a mean particle s ize of about 200 nm were obtained. From a ratio of phospholipid to dru g of 1:1 downwards, the systems became nearly transparent. The particl e 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 s ystems were described as bilayer-structured. At and below the ratio of 1:1, a mixed micelle was indicated. In the P-31-NMR spectra, the tran sformation is emphasized by both appearance and disappearance of signa ls. A model based on the theory of self-assembly is presented which ex plains the phase transformation due to drug amphiphilicity. Conclusion s. We predict that the model presented will hold in general only due t o the amphiphilic properties of the drug.