oa Editorial [Hot Topic: Physico-chemical Approach to Targeting Phenomena (Guest Editors: Sadao Hirota and Nejat Duzgunes)]

Drug targeting is one of the most important phenomena for therapies of diseases. The phenomena have been divided into two categories, passive targeting in which drug carriers circulate in the bloodstream and accumulate in a target tissue without any specific interactions, and active targeting in which drug carriers with ligands accumulate in a target tissue with receptors through ligand-receptor interactions. The enhanced permeation and retention (EPR) effect in drug delivery has been the subject of many studies on passive targeting of drugs, and has paved the way for nanoparticles and poly(ethylene glycol)-coupled liposomes as drug delivery systems (DDS). However, the physicochemical basis of many active targeting phenomena, including targeting of nanoparticles to particular cells or tissues, has not always been understood well. Clarifying this physicochemical basis may help drug delivery become more systematic, efficient and successful. Whereas passive targeting by EPR may depend on a large number of factors, only a few of them, such as particle size and charge, are usually determined quantitatively. Other factors should be considered. Two such factors are introduced in this issue. When the physicochemical factors of active targeting are characterized thoroughly, colloidal systems may be formulated and specified to satisfy these factors. Therefore, a better knowledge of kinetics and thermodynamics, colloid and surface phenomena, polymer science and rheology, may result in more successful active DDS. In this issue, exciting recent studies on the physical chemistry of targeting phenomena are reviewed by expert contributions. I. Meerovich et al. have made an attempt to analyze the main factors that influence the outcome from tissue or subcellular targeting on the kinetic or thermodynamic level. The different physicochemical mechanisms of cell-nanocarrier interactions are elucidated in thermodynamic terms, including Gibbs free energy and the binding constant. The problems related to kinetic modeling of targeted drug nanocarriers are also discussed in the review. H. Nabika et al. have applied surface chemistry to targeting of a lipid particle to a specific cell surface with a self-spreading lipid bilayer at the solid / liquid interface. K. Akiyoshi et al. have reported that a polysaccharide nanogel acts as an artificial molecular chaperone. Here, they report that a complex of nanogels with cancer antigen proteins triggers an immune response, and is useful as a method of cancer immunotherapy. G. M. Pavan et al. have constructed a virtual bridge between the design of cationic dendrimers and anionic DNA and siRNA macromolecules. T. Sato et al., who have studied the enhancement of pDNA transfection efficiency of pDNA/chitosan complexes with lactose- modified chitosan, have found that the morphologies of pDNA/chitosan complexes were largely affected by the molecular weight of chitosan and the stoichiometry of pDNA:chitosan. They have also found that cell transfection and resistance of pDNA against DNase were also affected by the morphology of the complexes. Y. Sun, in connection with the morphology of nonviral vectors, has determined rheologically the shape parameters of lipoplexes, and has shown that a flow incubation during the formation of lipoplexes from cationic lipids and DNA can control the shape of the resulting lipoplex. It is known that poly(ethylene glycol) modification of liposomal membranes forms a fixed aqueous layer and prevents the attraction of opsonins to the liposome. I. Sugiyama et al. have determined the thickness of the fixed aqueous layer (FALT) around liposomes and have shown that doxorubicin-containing liposomes increased the concentration of the drug in plasma and tumors according to the increase of FALT. S. Sakuma et al. have described a design concept for a nanoprobe, a peanut agglutinin-immobilized polystyrene nanosphere with surface poly(N-vinylacetamide) chains, encapsulating coumarin 6. The nanosphere has thus become an imaging agent that enables real-time and accurate diagnosis of small-sized colorectal tumors. The editors believe that this special issue will serve as a stimulus for future investigations into this potentially powerful approach to drug discovery technologies.