Research

Laboratory of Biointerface Chemistry

Professor Minoru Nakano, Ph.D.
Associate Professor Keisuke Ikeda, Ph.D.
Assistant Professor Hiroyuki Nakao, Ph.D.

The aim of the research in our laboratory is to develop a new field in pharmaceutical science by elucidating colloid chemical aspects of the heterogeneous, complex system of biocolloids based on the physical chemistry, to construct a rational methodology for developing new drugs harmonious with the complicate biocolloidal systems in our body, and to produce and educate researchers who can put above matters in practice. Especially, we are clarifying several intermolecular interactions on lipid membranes, such as biogenesis of lipoproteins and protein-mediated lipid transfer. In addition, we are developing new pharmaceuticals using lipid assemblies, such as liposomes, emulsions, cubosomes, and nanodiscs. Our current research projects are listed below.

Membrane-protein interaction and dynamics of membrane lipids
High-density lipoprotein (HDL) is a target for the development of new drugs for arteriosclerosis because of negative correlation between circulating levels of HDL and a risk of cardiovascular disease. However, the molecular mechanism by which HDL is formed is less well understood. We aim to elucidate this mechanism by physicochemical approaches with model lipid membranes. So far, we clarified that several changes in membrane environment facilitate spontaneous reconstitution of discoidal HDLs (nanodiscs) on the interaction with apolipoprotein A-I. We also developed a method to detect interbilayer and transbilayer transfers of phospholipids by means of time-resolved small-angle neutron scattering and revealed that nanodiscs represents a 20-fold higher lipid transfer than liposomes. We are now focusing on the quantitative analysis of protein-mediated lipid transport such as lipid transfer proteins and flippases, which are biologically important.

New lipid colloidal particulates
Lipid emulsion is used as a model compound of a plasma lipoprotein particle and it is applied to the drug delivery system. We found for the first time that emulsion binds apolipoproteins about 10-fold more than liposome. In consequence, the systemic catabolism of the particulates and their interaction with the cultured cell change remarkably. In addition, the colloidal particles having bicontinuous cubic structure (cubosome) and inverted hexagonal structure (hexosome) have been successfully prepared for the first time. Accordingly, we now focus on clarifying physical properties of the nonlamellar phases and their biophysical function. The development of their application for drug is also in progress.