Characterization of sodium dodecylsulphate and dodecylphosphocholine mixed micelles through NMR and dynamic light scattering.

The complexity of biological membranes leads to the use of extremely simplified models in biophysical investigations of membrane-bound proteins and peptides. Liposomes are probably the most widely used membrane models due, especially, to their versatility in terms of electric charge and size. However, liquid-state NMR suffers the lack of such a model, because even the smallest liposomes slowly tumble in solution, resulting in a dramatic signals broadening. Micelles are typically used as good substitutes, with sodium dodecylsulphate (SDS) and dodecylphosphocholine (DPC) being the most widely employed surfactants. However, they are always used separately to mimic prokaryotic and eukaryotic membranes, respectively, and accurate investigations as a function of surface charge cannot be performed. In this work, the critical micelle concentration (CMC) of binary mixtures with different SDS/DPC ratios has been determined by following the chemical shift variation of selected (1)H and (31)P NMR signals as a function of total surfactant concentration. The regular solution theory and the Motomura's formalism have been applied to characterize the micellization both in water and in phosphate buffer saline, and results were compared with those obtained directly from the experimental NMR chemical shift. The ζ-potential and size distribution of the mixed micelles have been estimated with dynamic light scattering measurements. Results showed that SDS and DPC are synergic and can be used together to prepare mixed micelles with different negative/zwitterionic surfactants molar ratio.

Lipid based liquid-crystalline stabilized formulations for the sustained release of bioactive hydrophilic molecules.

Lipid based formulations, endowed of long term stability as a result of the formation of lamellar liquid crystals, were prepared using the natural lipids lecithin and glycerol trioleate in water, and characterized using optical microscopy, SAXRD and NMR. The formulations, designed as possible carriers for lysozyme and caffeine, were evaluated for structural features and stability after the loading of the guest molecules. Release experiments were performed at 37 °C using the PBS medium. No burst release was observed either for lysozyme or caffeine. Although lysozyme released from the lipid formulations does not fully retain its biological activity, the investigated liquid crystal stabilized formulations display a promising potential as drug and cosmetic carriers for topical applications, due to their high biocompatibility.

Physicochemical, cytotoxic, and dermal release features of a novel cationic liposome nanocarrier.

A novel cationic liposome nanocarrier, having interesting performance in topical drug delivery, is here presented and evaluated for its features. Two penetration enhancers, namely monoolein and lauroylcholine chloride, are combined to rapidly formulate (15 min) a cationic liposome nanostructure endowed of excellent stability (>6 months) and skin penetration ability, along with low short-term cytotoxicity, as evaluated via the MTT test. Cytotoxicity tests and lipid droplet analysis give a strong indication that monoolein and lauroylcholine synergistically endanger long-term cells viability. The physicochemical features, investigated through SAXS, DLS, and cryo-TEM techniques, reveal that the nanostructure is retained after loading with diclofenac in its acid (hydrophobic) form. The drug release performances are studied using intact newborn pig skin. Analysis of the different skin strata proves that the drug mainly accumulates into the viable epidermis with almost no deposition into the derma. Indeed, the flux of the drug across the skin is exceptionally low, with only 1% release after 24 h. These results validate the use of this novel formulation for topical drug release when the delivery to the systemic circulation should be avoided.