Natural inspiration: Amphiphilic polysaccharide-block-polypeptide copolymers were synthesized by click chemistry from dextran end-functionalized with an alkyne group and poly(gamma-benzyl L-glutamate) end-functionalized with an azide group. The ability of these copolymers to self-assemble into small vesicles (see picture) suggests the possibility of a new generation of drug- and gene-delivery systems whose structure mimics that of viruses.

Objectives We aimed to evaluate gadopiclenol, a newly developed extracellular nonspecific macrocyclic gadolinium-based contrast agent (GBCA) having high relaxivity properties, which was designed to increase lesion detection and characterization by magnetic resonance imaging. Methods We described the molecular structure of gadopiclenol and measured the r 1 and r 2 relaxivity properties at fields of 0.47 and 1.41 T in water and human serum. Nuclear magnetic relaxation dispersion profile measurements were performed from 0.24 mT to 7 T. Protonation and complexation constants were determined using pH-metric measurements, and we investigated the acid-assisted dissociation of gadopiclenol, gadodiamide, gadobutrol, and gadoterate at 37°C and pH 1.2. Applying the relaxometry technique (37°C, 0.47 T), we investigated the risk of dechelation of gadopiclenol, gadoterate, and gadodiamide in the presence of ZnCl 2 (2.5 mM) and a phosphate buffer (335 mM). Pharmacokinetics studies of radiolabeled 153 Gd-gadopiclenol were performed in Beagle dogs, and protein binding was measured in rats, dogs, and humans plasma and red blood cells. Results Gadopiclenol [gadolinium chelate of 2,2′,2″-(3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-3,6,9-triyl)tris(5-((2,3-dihydroxypropyl)amino)-5-oxopentanoic acid); registry number 933983-75-6] is based on a pyclen macrocyclic structure. Gadopiclenol exhibited a very high relaxivity in water (r 1 = 12.2 mM −1 ·s −1 at 1.41 T), and the r 1 value in human serum at 37°C did not markedly change with increasing field (r 1 = 12.8 mM −1 ·s −1 at 1.41 T and 11.6 mM −1 ·s −1 at 3 T). The relaxivity data in human serum did not indicate protein binding. The nuclear magnetic relaxation dispersion profile of gadopiclenol exhibited a high and stable relaxivity in a strong magnetic field. Gadopiclenol showed high kinetic inertness under acidic conditions, with a dissociation half-life of 20 ± 3 days compared with 4 ± 0.5 days for gadoterate, 18 hours for gadobutrol, and less than 5 seconds for gadodiamide and gadopentetate. The pharmacokinetic profile in dogs was typical of extracellular nonspecific GBCAs, showing distribution in the extracellular compartment and no metabolism. No protein binding was found in rats, dogs, and humans. Conclusions Gadopiclenol is a new extracellular and macrocyclic Gd chelate that exhibited high relaxivity, no protein binding, and high kinetic inertness. Its pharmacokinetic profile in dogs was similar to that of other extracellular nonspecific GBCAs.

International audienceA thermoresponsive hybrid system for drug delivery purposes is designed by modifying the surface of silica-coated magnetic lanthanum strontium manganite nanoparticles with block copolymers following a non-covalent approach. Block copolymers containing a short poly(L-lysine) segment and a polyether segment of varying composition are adsorbed through electrostatic interactions between positively charged lysine units and negatively charged SiO− groups at the silica surface, giving rise to mixed polyether brushes with a good control over the chain surface density and thickness of the polymer layer. The thermoresponsiveness of the assemblies is controlled by the ethylene oxide/propylene oxide ratio in the polymer brush and the corresponding LCST of the polyether blocks. Important parameters like the aggregation temperature of the particles can be finely adjusted by modifying this ratio. The polarity of the polymer layer can also be varied to maximize the encapsulation efficiency of a moderately hydrophobic drug like doxorubicin. Drug release experiments are performed by taking advantage of the ac magnetically induced heating properties of the magnetic core to speed up the release of doxorubicin owing to structural changes within the polyether brush