**3. Top-down and bottom-up approaches in processes**

In general, the processes for producing nanomaterials can be characterized as two main approaches, top-down or bottom-up. The top-down approach starts with large particles that are comminuted to a nanometric size through the application of high-energy forces. This is the classical approach for the majority of nanoparticle production processes. Top-down approaches require highly precise control of the variables of the process in order to obtain the narrow particle size (Mijatovic et al., 2005). Lithography is the classical example. Other high-energy processes include grinding, high impact homogenization, ultrasound waves, and extrusion through nanoporous membranes (Sanguansri & Augustin, 2006).

Bottom-up approaches are based on the self-organization of molecules under thermodynamic control, generating nanostructures from atoms and molecules as a result of the effects of the chemical, physical, and process interventions on the balance of the intermolecular and intramolecular forces of the system components (Sanguansri & Augustin, 2006). Bottom-up approaches focus on the construction of functional materials, mimetizing the hierarchic organization of the molecules in live organisms, though the science still does not dominate the complex auto-aggregate structures in nature.

Regarding liposome production, top-down approaches comprise the high-energy comminution of a polydispersed population of multilamellar liposomes formed under noncontrolled aggregation. The bottom-up approach manipulates the phospholipid molecules in controlled local aggregation in space and time, generating a monodispersed population of nano-sized unilamellar liposomes. Figure 3 illustrates top-down and bottom-up approaches for liposome production.

Fig. 3. Scheme of top-down and bottom-up approaches for liposome production.
