**2. Methodology**

release of bioactive compounds. To achieve that, novel nanomaterials have improved, thanks to the rapid advances in material sciences, many of them with tunable properties that allow the controlled release of drugs [4]. Such nanoparticulated systems include polymeric micelles, polymer-DNA complexes, nanogels, lipid-based (liposomes, nanostructured lipid carriers) substances, and macrocyclic carriers (cyclodextrins, calixarenes), among others. DDS provide an extraordinary opportunity for the safe and efficient release of drugs, genes, and a great variety of molecules. The incorporation of nanomaterials confers physical advantages such as improved drug solubility, decreased degradation or clearance rates, decreased systemic toxicity, and improved clinical efficacy to the nanoformulations [5]. Furthermore, the sustained release of the drugs allows one to reduce the frequency of drug administration or even the dose. Finally, the process time for approval of a novel DDS that carries a drug already sanctioned by the regulatory agents is shorter, making the development process less expensive.

Relevant information on the system can be obtained using computer simulations at very different lengths and time scales: moving from continuous to the atomistic level. In this context, knowledge of the mechanism of drug encapsulation and release at the atomic/molecular level can help in the design of nanomedicines, according to the desired objective and for each spe-

In this sense, techniques that access the molecular level, such as molecular dynamics (MD) and Monte Carlo simulations, are very powerful tools to understand biomolecular processes [6, 7]. In particular, classical MD simulations could help in the development/improvement of drug delivery systems. But, at the current computer capacity, not all nanoparticles can be studied by MD, at their full length. How to approach to this problem? For instance, liposomes are widely used DDS, consisting of spherical lipid-based vesicles whose diameters range from 30 nm to several micrometers. To simulate this kind of DDS carrier there are two possible approaches, depending on the question to answer: (i) considering a big liposome, that is, having an infinite radius, one can use planar bilayers or also simulate just a section of the vesicle, within periodic boundary conditions and (ii) on the other hand, a small liposome can be fully treated. This is exemplified in **Figure 1**. Broadly, we can access atomic details of drug-bilayer interaction using atomic level MD, but liposomes are better signified using

**Figure 1.** Schematic representation of the section of the vesicle bilayer and small liposome used as model for atomistic

cific case.

74 Molecular Dynamics

coarse grain (CG) models.

and coarse grain simulations.

The molecular dynamics technique has a long history [8] and it nowadays constitutes a very important theoretical tool in physics, chemistry, biology, and related disciplines. Thanks to the growing development of computing power, the MD technique is renewed continuously, allowing one to study larger and more complex systems and problems [8].
