DESIGN OF NEW SMART DRUG DELIVERY NANOVEHICLES
Nanostructures have the potential to revolutionize a wide range of medical diagnostic and therapeutic interventions such as diagnostic imaging, nucleic acid delivery, implantable devices and, of particular interest, drug delivery. The development of drug delivery nanocarriers brings new challenges related to the needs of overcoming the deficient solubility/stability of a large number substances of both synthetic and biotechnological origin, improving the efficiency and safety profiles of old drugs as a way to extend their therapeutic and commercial value as well as conferring protection, control the release and/or even target the intended cargo molecules to the site of action.Due to their small sizes, the nanocarriers exhibit unique physicochemical and biological properties (e.g., an enhanced reactive area as well as an ability to cross cell and tissue barriers) that make them a
favourable material for drug delivery applications. Their nanosize also promotes an uptake by cells more easily than larger molecules. By nanovehicles, the therapeutic molecule is transported to the site of action, thus its influence on healthy tissues and cells and undesirable side effects can be minimized. A wide variety of drugs can be delivered using nanoparticulate carriers via a number of routes: Nanovehicles can be used to deliver hydrophilic drugs, hydrophobic drugs, proteins, peptides and nucleic acids. Additionally, different strategies have been proposed to regulate the association and, consequently, the drug release playing with the materials used to produce the nanocarriers as well as with the structural design of the system. Nanocarriers also protect the cargo from rapid degradation or clearance and enhance drug concentration in target tissues, therefore, lower doses of the drug are required. In addition to their controlled or triggered release properties, nanocarriers can also be designed to afford longer circulation times, reducing unwanted distribution and promoting targeting the site of action. In this context, carrier´s functionalization, resulting in a stealth surface avoiding the opsonisation phenomenon (adhesion of serum proteins at the nanoparticles surface), is necessary to increase circulation times by escaping the mononuclear phagocyte system. Hence, our research group possess a long experience devoted to the obtention of new drug delivery nanocarriers based on polymeric micelles, vesicles and nanogels, protein/polymeric capsules and nanoparticles, solid lipid nanoparticles and liposomes, and composite hybrid nanoparticulate carriers. A great part of these nanovehicles are triggered under internal (pH, temperature, enzymes…) and/or external (light, alternating magnetic fields) stimuli to control cargo release into cells, which can be targeted either by passive (enhanced permeation and retention effect, EPR) or active (nanocarriers surface biofunctionalization with suitable targeting ligands to receptors overexpressed on unhealthy cells/tissues) means.