Dendrimer nanocarriers drug action: perspective for neuronal pharmacology.

Abstract

General aspects: Currently, several strategies have been used to overcome common problems found in pharmacological therapies, such as insolubility, reduced bioavailability and low specificity of drugs. One of the most promising alternatives proposed is the use of dendrimeric drug nanocarriers, polymeric chemical structures of diverse nature that contain, transport and deliver the desired drug in biological systems. One of the dendrimers that has been most successfully used is based on polyamidoamine (PAMAM). PAMAM are organized from a central molecule of ethylenediamine that gives way to expansive growing layers (generations) terminating in a surface of primary amines that are positively charged at physiological pH. This architecture determines the presence of intramolecular cavities that allow the encapsulation of drugs and their release (Figure 1). Alternatively, drugs can also be associated to the dendrimer surface. Among the main advantages of PAMAM dendrimers is their high solubility, stability and efficient encapsulation of different drugs, in addition to its easily modifiable surface. This latter feature allows the linking of several chemical groups and molecules to the surface amino groups in order to improve their properties, such as surface charges, encapsulation capacity and drug delivery, ligand linkage to reach a specific target tissue, among other applications (Svenson, 2009). The versatility of the PAMAM dendrimers has demonstrated to be useful in studying the action of several drugs of high biomedical impact. Thus, anticancer, anti-inflammatory and antimicrobial agents, among others, have been tested with promising results (Svenson, 2009). However, the pharmaceutical use of such systems in neuropathology is a field that is yet to be explored.