Scientific research activities

Nanomedicines are mainly developed for control of the pharmacokinetics (including biodistribution). Therefore, the analysis of the relation between quality attributes and biodistribution including intracellular trafficking of nanomedicines is focused in this research. Knowledge about the relationship between biodistribution and biological effects of nanomedicines, that include a therapeutic and adverse one, is also very important to decide which quality attributes are critical.


Physicochemical characterization of nanomedicines
・Development of methods to measure the physicochemical properties of nanometer-size components in drugs.
・Identification of critical quality attributes which affect the biodistribution of nanomedicines.
・Application of QbD strategy to nanomedicines
・Comparability assessment of nanomedicines subject to change in their manufacturing

Related publications in the scientific journals
・“Imaging and size measurement of nanoparticles in aqueous medium by use of atomic force microscopy. Anal. Bioanal. Chem. 410, 1525-1531 (2018) New
・“Control of liposomal penetration into three-dimensional multicellular tumor spheroids by modulating liposomal membrane rigidity” Mol. Pharm. 14, 2158-2165 (2017)
・“Membrane rigidity determined by atomic force microscopy is a parameter of the permeability of liposomal membanes to the hydrophilic compound calcein.” AAPS PharmSci Tech 18, 1887-1893 (2017)
・“Evaluating the properties of poly (lactic-co-glycolic acid) nanoparticle formulations encapsulating a hydrophobic drug by using the Quality by Design approach. ” Chem. Pharm. Bull. 65, 218-228 (2017).
・“Atomic force microscopic analysis of the effect of lipid composition on liposome membrane rigidity.” Langmuir 32, 6074-6082 (2016).
・“Observation of liposomes of differing lipid composition in aqueous medium by means of atomic force microscopy.” Microscopy (Oxf) 65, 383-389 (2016).
・“General cinsiderations regarding the in vitro and in vivo properties of block copolymer micelle products and their evaluation.” J. Control. Release 210, 76-83 (2015).
・“Size separation and size determination of liposomes.” J. Sep. Sci. 34, 2861-2865 (2011).
・“Size separation of colloidally dispersed nanoparticles using a monolithic capillary column.” J. Chromatogr. A　1218, 5520–5526 (2011).
・“Controlled structure and properties of silicate nanoparticle networks for incorporation of biosystem components” Nanotechnology 22, 205702 (2011).


In vitro and in vivo assays of biodistribution of nanomedicines
・Research on the evaluation of in vitro/in vivo stability, targeting, and active substances release of nanomedicines
・Development of method to trace the intracellular trafficking of nanomedicines using imaging techniques

Related publications in the scientific journals
・“Involvement of scavenger receptor class B type 1 and low-density lipoprotein receptor in the internalization of liposomes into HepG2 cells.” Biochim Biophys Acta. 1859, 2253-2258 (2017).New
・“Effect of knockout of Mdr1a and Mdr1b ABCB1 genes on the systemic exposure of a doxorubicin-conjugated block copolymer in mice.” Mol. Pharm. 12, 3175-3183 (2015).
・Leading Opinion “Elucidating the molecular mechanism for the intracellular trafficking and fate of block copolymer micelles and their components ” Biomaterials 35, 1347-1358 (2014).
・“Intracellular trafficking mechanism, from intracellular uptake to extracellular efflux, for phospholipid/cholesterol liposomes. ” Biomaterials 33, 8131-8141 (2012).
・“Evaluation of intracellular trafficking and clearance from HeLa cells of doxorubicin-bound block copolymers.” Int. J. Pharm. 423, 401– 409 (2012)
・"Rapid and sensitive method for measuring the plasma concentration of doxorubicin and its metabolites" Chem. Pharm. Bull. 60(3), 391-396 (2012).
・“Analysis of intracellular doxorubicin and its metabolites by ultra-high-performance liquid chromatography” J. Chromatogr. B., 878, 1466-1470 (2010)


In vitro and in vivo assays to assess safety of nanomedicines
・Research on the immunoreactivity of nanomedicines
・Research on the in vitro intestinal permeability properties and intestinal cell toxicity of nanoparticles

Related publications in the scientific journals
・“Cell type-specific responses of peripheral blood CD14-positive monocytes to liposome-encapsulated immunostimulatory siRNA.” Biol. Pharm. Bull. 39, 1859-1867 (2016) .
・“Physicochemical properties and in vitro intestinal permeability properties and intestinal cell toxicity of silica particles, performed in simulated gastrointestinal fluids.” Biochim. Biophys. Acta, 1840, 1171-1180 (2014).


Participation in human resource exchange programs with academia

Objects
・Enhancement of human resource exchange among academia and NIHS/PMDA
・Establishment of evaluation methods for safety and efficacy based on regulatory science

Nanotechnology-related project (FY2012-2016)
Academia
・Hokkaido University
・The University of Tokyo
National Cancer Center