ABSTRACT

The addition of detergents to artificial lipid bilayers and liposomes induces the formation of a number of intermediates [mixed vesicles (MVs) and various types of mixed micelles (MMs)], which, besides their interesting physicochemical properties, attract more and more attention as potential nanocarrier systems for the delivery and/or solubility of drugs (1,2). In dermatological research, for example, such nanocarriers were used to increase skin penetration and thus transdermal drug delivery (3). Technical terms associated with these endeavors are surfactant-based elastic vesicles and Transfersomes1 (4-6). Depending on the lipid to detergent ratio, various intermediate structures can be found: MVs, bilayered phospholipids fragments (BPFs), cylindrical mixed micelles (CMMs), lipid-rich spherical or ellipsoidal mixed micelles (SMMs or EMMs) and at low lipid to detergent ratios lipid-poor MMs are formed (7). The existence of these structures was confirmed and made visible by using techniques like freeze-fracture electron microscopy (FFEM) and cryo transmission electron microscopy (cryo-TEM). The stability and formation of the different structures is governed by their thermodynamic properties (8,9). In the presented paper, isothermal titration

calorimetry (ITC) is used to study the stoichiometry as well as the thermodynamic properties of the detergent to lipid interactions and stability of the formed mixed systems. The latter is the main focus of this discussion. Different ITC experiments are presented for studying phospholipids-detergent interactions, accompanying the partitioning of detergent molecules in to the lipidic phase of vesicles and the formation of MVs (10). From these results, a complete thermodynamic picture of the mixed system formation is derived. The obtained information allows a deeper insight and understanding with respect to the formation of mixed systems and their thermodynamic stability. Additionally, various selected biophysical methods for the characterization of mixed lipiddetergent systems are briefly discussed. The chapter ends with considering the pharmaceutical aspects of these nano carriers for future drug delivery systems.

DETERGENTS, LIPIDS, AND WATER