Annual Report of Cosmetology vol.31, 2023
Synopsis of Original Research Paper

Development of Functional Hydrophilic Colloids
Containing Many Water Molecules
Satoru Karasawa
Showa Pharamaceutical University

Hydrophilic-gels and -nanoparticles are paid much attention in medicinal and cosmetic
fields. Especially in the field of contrast agents such MRI, fluorescence and RI, the functional
nanoparticles, which form approximately 100 nm size in solutions, are passively accumulated
in tumor tissues, thus many researchers have reported the tumor-accumulating nanoparticles
based on the 100 nm. This tumor-accumulating behavior utilizing the nanoparticles is known
as Enhanced Permeability Retention (EPR) effect. Moreover, there is a deep relationshipbetween MRI contrast agents and water molecules; the high contrast ability is derived
from presence of many water molecules around the contrast agents. Thus, the hydrophilic
nanoparticles, in which many water molecules are taken the core of the particle into, arepromising as MRI contrast agents with a high contrast ability. We have studied on the MRI
contrast agents utilizing the organic radical. Because the typical MRI contrast agents inclinical, which are consisted of Gadolinium ions (Gd) as a metal spin source, have someissues; renal disorder and brain accumulation by an excess usage. Accordingly, instead ofGd ion, the metal free contrast agents consisting of organic radical are planned. This time,
three nanoparticles consisted of radical species are prepared and the physical parameters suchrotational correlation time (τR) bases on the ESR signal intensity and width, T1-weighed image
with T1-relaxation time, hydrodynamic diameter (DH) by a dynamic light scattering (DLS), andmorphology observations of nanoparticles using a transmission electron microscopy (TEM).
Due to checks of the hydrophilicity of the nanoparticles, ClogP values of the nanoparticles
were calculated by a ChemDraw Professional 16.0.
Three nanoparticles with organic radicals, RNP-OTHP, -OH, and OAc, were preparedaccording to a previous our report. In the DLS of the aqueous solutions, D H values for all
RNP-X showed the similar 100 - 200 nm size-distribution. In contrast, TEM images ofRNP-OH and -OTHP showed the different morphology; film-like particles and sphericalparticles, for RNP-OTHP and –OH, suggesting that the former and latter are vesicle-like andmicelle-like particles, respectively. In the contrast agent ability, the relaxivities (r1) of RNPOH and -OAc, which are calculated by a slope of the plot of inverse T1 relaxation times vsconcentration of contrast agents, showed 0.17 and 0.31 mM-1s-1, respectively, indicating thatthe latter is more than 1.7 time larger than that of the former, and the highest value among
the radical nanoparticles reported by our group. To reveal the relationship between r1 valueand hydrophilicity, ClogP values were estimated to be -0.38 and 1.4 for RNP-OH and -OAc,
respectively. In the previous our report, the micelle-like nanoparticle, PRO2, possesses thesmaller ClogP (-0.037) and r1 (0.17 mM-1s-1) values rather than those of RNP-OAc. The abovementioned results indicate that the morphology of the nanoparticles are control by the ClogP
value: the value of approximately 1.0 as a borderline, the nanoparticles with the smaller andlarger ClogP value rather than 1.0, would form the micelle and vesicle-like morphology.
Accordingly, the vesicle-like nanoparticle based on own ClogP value caused the high r1 valueof RNP-OAc.
Considering the above-mentioned results, by controlling the suitable ClogP value, theconstruction of the metal-free MRI contrast with the high contrast ability (relaxivity: r1) isunderway.
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