Critical assembly concentration

Micelles the mostly spherical nanoscale aggregates formed by amphiphilic compounds above their critical micelle concentration in aqueous solution have a narrow size distribution and are dynamic, because there is a fast exchange of amphiphiles in solution and those incorporated in micelles. However, micelles are defined as self-assembled structures, since the structure is in thermodynamical equilibrium. 

The value of EM for a cooperative self-assembled structure provides a measure of the monomer concentration at which trivial polymeric structures start to compete, and therefore EM represents the upper limit of the concentration range within which the cooperative structure is stable (Scheme 2). The lower limit of this range is called the critical self-assembly concentration (csac) and is determined by the stoichiometry of the assembly and the strength of the non-covalent binding interactions weaker interactions and larger numbers of components raise the csac and narrow the stability window of the assembly (8). Theoretical treatments of the thermodynamics of the self-assembly process have been reported by Hunter (8), Sanders (9), and Mandolini (10). The value of EM is lowered by enthalpic contributions associated with... 

The simplest way in which a process occurs by itself is when it is under thermodynamic control. The folding of a protein, or the self-assembly of micelles at the critical micelle concentration (cmc) are examples of spontaneous processes the latter are characterized by a negative free-energy change, as the self-orgaiuzed product has a lower energy than the single components. ... 

Figure 5.3 Self-assembly of a vesicle. Water-soluble molecules can be entrapped inside, ionic molecules on the polar head groups of the surface, amphiphatic molecules in the hydrophobic bilayer, (cac critical aggregate concentration).

Surfactants having a positive curvature, above a given concentration usually called the critical micellar concentration, cmc, self-assemble to form oil-in-water aggregates called normal micelles. The surfactant most often used is sodium dodecyl sulfate, Na(DS) or SDS. To make particles, the counterion of the surfactant is replaced by ions which participate in the chemical reaction. These are called functionalized surfactants. 

Several major barriers need to be overcome for the development of nonviral gene delivery systems into true therapeutic products for use in humans. These barriers fall into three classes manufacturing, formulation, and stability (extracellular barriers and intracellular barriers) (85). Cationic lipids and cationic polymers self-assemble with DNA to form small particles that are suitable for cellular uptake. At the therapeutic doses positively charged particles readily aggregate as their concentration increases, and are quickly precipitated above their critical flocculation concentration. 

In contrast to the above-described kinetic stability, colloids may also be thermodynamically stable. A stable macromolecular solution is an example we have already discussed. Formation of micelles beyond the critical micelle concentration is another example of the formation of a thermodynamically stable colloidal phase. However, when the concentration of the (say, initially spherical) micelles increases with addition of surfactants to the system, the spherical micelles may become thermodynamically unstable and may form other forms of (thermodynamically stable) surfactant assemblies of more complex shapes (such as cylindrical micelles, liquid-crystalline phases, bilayers, etc.). 

Micelles are colloidal dispersions that form spontaneously, under certain concentrations, from amphiphilic or surface-active agents (surfactants), molecules of which consist of two distinct regions with opposite afL nities toward a given solvent such as water (Torchilin, 2007). Micelles form when the concentration of these amphiphiles is above the critical micelle concentration (CMC). They consist of an inner core of assembled hydrophobic segments and an outer hydrophilic shell serving as a stabilizing interface between the hydrophobic core and the external aqueous environment. Micelles solubilize molecules of poorly soluble nonpolar pharmaceuticals within the micelle core, while polar molecules could be adsorbed on the micelle surface, and substances with intermediate polarity distributed along surfactant molecules in intermediate positions. 

Pronounced self-assembly of 281 and 282 in nonpolar solvents (e.g., aliphatic and aromatic hydrocarbons) takes place as a result of hydrogen bonding between amide groups to result in the formation of gels above a critical gelation concentration. 

Amphiphilic molecules (surfactants) can assemble into nanoscopic supramolecular structures with a hydrophobic core and a hydrophilic shell micellar arrangement. As surfactant concentration is increased in aqueous solutions, the separated molecules aggregate into micelles upon reaching a concentration interval known as the critical micellar concentration (CMC). 

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