Do not tumble dry: Gadolinium-DOTA encapsulated into polysaccharide nanoparticles (GdDOTA NPs) exhibited high relaxivity (r(1) =101.7 s(-1) mM(-1) per Gd(3+) ion at 37 °C and 20 MHz). This high relaxation rate is due to efficient Gd loading, reduced tumbling of the Gd complex, and the hydrogel nature of the nanoparticles. The efficacy of the nanoparticles as a T(1)/T(2) dual-mode contrast agent was studied in C6 cells.

A series of hydrogel nanoparticles incorporating MRI contrast agents (GdDOTP and MS325) as potential cross-linkers were elaborated by an easy and robust ionotropic gelation process.

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Chitosan CS-tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA ⊂ CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter ϕ < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8). Characterization of NG size distribution by dynamic light scattering (DLS) and asymetrical flow-field-flow-fractionation (AF4) showed discrepancies since DLS diameters were consistently above 200 nm while AF4 showed individual nano-objects with ϕ < 100 nm. Such a difference could be correlated to the presence of aggregates inherent to ionic gelation. This point was clarified by atomic force microscopy (AFM) in liquid mode which highlighted the main presence of individual nano-objects in nanosuspensions. Thus, combination of DLS, AF4 and AFM provided a more precise characterization of GdDOTA ⊂ CS-TPP/HA nanohydrogels which, in turn, allowed to select formulations leading to NGs of suitable mean sizes showing good MRI efficiency and negligible toxicity.

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Etoposide (VP-16) is a hydrophobic anticancer agent inhibiting Topoisomerase II, commonly used in pediatric brain chemotherapeutic schemes as mildly toxic. Unfortunately, despite its appropriate solubilization in vehicle solvents, its poor bioavailability and limited passage of the blood-brain barrier concur to disappointing results requiring the development of new delivery system forms. In this study, etoposide formulated as a parenteral injectable solution (Teva®) was loaded into all-biocompatible poly(lactide-co-glycolide) (PLGA) or PLGA/P188-blended nanoparticles (size 110-130 nm) using a fully biocompatible nanoprecipitation technique. The presence of coprecipitated P188 on encapsulation efficacies and in vitro drug release was investigated. Drug encapsulation was determined using HPLC. Inflammatory response was checked by FACS analysis on human monocytes. Cytotoxic activity of the various simple (Teva®) or double (Teva®-loaded NPs) formulations was studied on the murine C6 and F98 cell lines. Obtained results suggest that, although noninflammatory neither nontoxic by themselves, the use of PLGA and PLGA/P188 nanoencapsulations over pre-existing etoposide formulation could induce a greatly improved cytotoxic activity. This approach demonstrated a promising perspective for parenteral delivery of VP16 and potential development of a therapeutic entity.

Because of its sub-millimeter spatial resolution, the noninvasive nature of the examinations, and the absence of ionizing radiation, magnetic resonance imaging (MRI) is an important diagnostic imaging tool. However, this technique suffers from low detection sensitivity. To improve this aspect, millimolar concentrations of paramagnetic contrast agents (CAs) are often administered prior to examination, to enhance the image contrast and thus, to highlight pathological areas. The most commonly used CAs are gadolinium complexes (GdCAs). [1,2] GdCAs do not directly provide a signal, but they shorten the T 1 and/or T 2 relaxation times of water protons in the tissues. [1] Their efficiency is measured in terms of relaxivity r 1 , which is defined as the relaxation rate enhancement of the water proton per millimolar metal ion. Until recently, all GdCAs were considered safe; unfortunately, it has been demonstrated that some of them may trigger the development of nephrogenic systemic fibrosis (NSF) in patients with renal failure. [3] Improvement is therefore needed to increase the relaxivity of known, low-risk GdCAs to decrease the injected doses. The interpretation of SBM theory [4] gives some guidelines on how to amplify r 1 . For applications at 0.5-1.5 T, high relaxivity can be achieved by high payload of active magnetic centers, by controlling the tumbling motion of the GdCAs, and by ensuring optimal water residency times in the gadolinium coordination sphere. [5] In this challenging area, recent progress has been achieved with the integration of gadolinium chelates into nanoparticles. For this purpose, many nanoparticles have been developed (modified natural nanoparticles, [6] liposomal nanoparticles, [6] micelles, [6] metal-organic frameworks, [7] fullerenes, [8] inorganic nanoparticles [9] ) but the predicted high relaxivities (on the order of 100 mm À1 s À1 ) have rarely been obtained. [9c-e] In this respect, our goal herein was to develop a new and straightforward synthesis of high-relaxivity gadolinium nanoparticles for MRI applications, with optimized nanoparticle production characteristics, gadolinium loading, and relaxivity at the same time. To take the risk of NSF disease into account, we choose to encapsulate a well-known, low-risk CA, [GdDOTA] À (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; the GdCA of DOTAREM). Because of its hydrophilic nature, the encapsulation of [GdDOTA] À was made in a hydrophilic polymer matrix. For biocompatibility reasons, chitosan (CH) [10] and hyaluronic acid (HA) [11] were chosen for the polymer matrix. CH is a positively charged, biocompatible polysaccharide composed of N-acetylglucosamine and glucosamine residues. HA is a natural, non-toxic, negatively charged polymer composed of glucuronic acid and N-acetylglucosamine residues. Herein, the

The treatment of stainless steel surfaces with responsive polymers was investigated using X-ray photoelectron spectroscopy and scanning electron microscopy. Poly(N-isopropylacrylamide) (PNIPAAM) is a temperature-sensitive polymer which is soluble in water below 32 • C (Lower Critical Solubility Temperature (LCST)) but collapses and aggregates above 32 • C. This polymer was adsorbed at 50 • C from solutions at different concentrations, followed by rinsing and different drying procedures. Thereby, a large variety of surface structures could be obtained, from smooth films to surfaces showing marked relief features due to residues of PNIPAAM aggregates. Two poly(styrene)-b-poly(acrylic acid), PS-PAA, with different block lengths, were spin-coated on stainless steel and showed preferential exposure of PS blocks at the outermost surface. PNIPAAM-conditioning was shown to strongly reduce yeast cell adhesion and to facilitate the removal of oil soil due to its high water affinity and chain mobility below the LCST. PS-PAA coatings also reduced yeast cell adhesion; this may partly be due to a reorganization of the surface, leading to exposure of PAA chains in contact with water and thus to electrostatic repulsion of the yeast cells.