[Kamat2010]

Nanotechnology has opened up a new area of research for the disease diagnosis as well as therapeutics. Though drug discovery is very essential for the proper treatment of the diseases, drug delivery remains a major concern. The agents used for drug delivery have been found to possess their own properties of cell toxicity, low persistence in the microenvironment of the body as well as impermeability across the cell membranes, which result in inefficient drug delivery within the body. Nanoparticles have emerged, as a better alternative for drug delivery in recent times though further in-depth research is essential to provide concrete evidence for the same.

Nanoparticles are usually made of elements, which are biologically less reactive and hence used for different diagnostic assays as well as therapies. The nanoparticles due to their extreme small size, zeta potential and other favourable factors have added advantage in being used as drug delivery agents. Adsorption of the proteins like antibodies or other bioactive moieties on the surface of the nanoparticles is a method by which the bioactive agents are transported to the target site in-vivo, but this method has some disadvantages because of which surface functionalization has gained importance. The adsorption on the surface technique causes the denaturation of the protein adsorbed in most of the cases and the presence of steric hindrance is one more drawback. Moreover, the nanoparticles must have to be present in the systemic circulation for a longer period. All these factors have initialized the study of surface functionalization of nanoparticles, which has become a greatly researched topic.

Surface functionalization means the introduction of chemical functional groups on the surface of the nanoparticles. The chemical groups are not directly attached to the nanoparticles but are attached using spacer arms or other lipophilic agents. Many studies have been conducted whereby PEG (Polyethylene glycol) has been used for the surface functionalization of the nanoparticles. The surface functionalized nanoparticles become capable of crossing the lipid bio layer of the membranes of the cell and thereby help in the delivery of the drugs and other bioactive agents to the target site in-vivo. The PEG spacer allows the GNPs (Gold nanoparticles) to persist in the systemic circulation within the body protected from the macrophage attack while providing flexibility also to the molecule for proper interaction with the target. Research with other surfactants apart from PEG, which can provide the same advantages as PEG in the drug delivery through nanoparticles is going on.

Surface functionalization is possible for carbon nanotubes (CNTs) also apart from GNPs. The CNTs have two ends and two surfaces (inner and outer). Hence, it provides wide possibility for functionalization on its surface thereby providing a possibility of delivery of bioactive agents within the body. The functionalization of the CNTs occurs usually by the physical adsorption of the surfactants by weakening of the van der Waals interaction within the bundle of CNTs, which may lead to the exfoliation of the CNTs. The exact mechanism of the adsorption and the nature of interaction between the CNTs and the surfactant remain unknown, though, it is suggested that in some cases the polymer coils itself around the CNTs in a helical fashion.

The surface functionalization of the nanoparticles has made tremendous progress in drug delivery through BBB. The potential drugs used for the therapy of the CNS related diseases face an enormous challenge of crossing the BBB due to which much progress in the successful treatment of the CNS related diseases has not been made. This problem has been resolved largely with the use of functionalized nanoparticles. Many possible mechanisms have been reported for the delivery of the drugs through the BBB with the use of nanoparticles. Endocytosis or transcytosis of the endothelial cell layer, dissolution of the membrane lipids of BBB due to surfactant effect, loosening of tight junctions of BBB due to the nanoparticle effect or the modification of the efflux protein in BBB thereby preventing efflux , may be some of the mechanisms by which the drug-coated nanoparticles move across BBB. Many other mechanisms have been suggested, which need proper concrete evidence as proof for the same. In this way, it is seen that surface functionalization of the nanoparticles has broadened the research related to drug delivery.