HEMA-Lysine-Based Cryogels for Highly Selective Heparin Neutralization.

Unfractionated heparin (UFH) and its low-molecular-weight fragments (LMWH) are widely used as anticoagulants for surgical procedures and extracorporeal blood purification therapies such as cardiovascular surgery and dialysis. The anticoagulant effect of heparin is essential for the optimal execution of extracorporeal blood circulation. However, at the end of these procedures, to avoid the risk of bleeding, it is necessary to neutralize it. Currently, the only antidote for heparin neutralization is protamine sulphate, a highly basic protein which constitutes a further source of serious side events and is ineffective in neutralizing LMWH. Furthermore, dialysis patients, due to the routine administration of heparin, often experience serious adverse effects, among which HIT (heparin-induced thrombocytopenia) is one of the most severe. For this reason, the finding of new heparin antagonists or alternative methods for heparin removal from blood is of great interest. Here, we describe the synthesis and characterization of a set of biocompatible macroporous cryogels based on poly(2-hydroxyethyl methacrylate) (pHEMA) and L-lysine with strong filtering capability and remarkable neutralization performance with regard to UFH and LMWH. These properties could enable the design and creation of a filtering device to rapidly reverse heparin, protecting patients from the harmful consequences of the anticoagulant.

In Vitro and In Vivo Safety of Hyaluronic Acid-Decorated Microparticles for Intravitreal Injection of Palmitoylethanolamide, Citicoline, or Glial-Cell-Derived Neurotrophic Factor.

The treatment of posterior eye segment diseases through intravitreal injection requires repeated injections of an active molecule, which may be associated with serious side effects and poor patient compliance. One brilliant strategy to overcome these issues is the use of drug-loaded microparticles for sustained release, aiming at reducing the frequency of injections. Therefore, the aim of this work was to assess the safety features of poly(lactic-co-glycolic acid) (PLGA)-based, hyaluronic acid-decorated microparticles loaded with palmitoylethanolamide (PEA), citicoline (CIT), or glial-cell-derived neurotrophic factor (GDNF). Microparticles were prepared by double emulsion-solvent evaporation and fully characterized for their technological features. Microparticles possessed a satisfactory safety profile in vitro on human retinal pigment epithelial (ARPE-19) cells. Interestingly, the administration of free GDNF led to a loss of cell viability, while GDNF sustained release displayed a positive effect in that regard. In vivo results confirmed the safety profile of both empty and loaded microparticles. Overall, the outcomes suggest that the produced microparticles are promising for improving the local administration of neuroprotective molecules. Further studies will be devoted to assess the therapeutic ability of microparticles.

Solid-State Preparation and Characterization of 2-Hydroxypropylcyclodextrins-Iodine Complexes as Stable Iodophors.

The use of iodine as antiseptic poses some issues related to its low water solubility and high volatility. Stable solid iodine-containing formulations are highly advisable and currently limited to the povidone-iodine complex. In this study, complexes of molecular iodine with 2-hydroxypropyl α-, ß- and γ-cyclodextrins were considered water-soluble iodophors and prepared in a solid state by using three different methods (liquid-assisted grinding, co-evaporation and sealed heating). The obtained solids were evaluated for their iodine content and stability over time in different conditions using a fully validated UV method. The assessment of the actual formation of an inclusion complex in a solid state was carried out by thermal analysis, and the presence of iodine was further confirmed by SEM/EDX and XPS analyses. High levels of iodine content (8.3-10.8%) were obtained with all the tested cyclodextrins, and some influence was exerted by the employed preparation method. Potential use as solid iodophors can be envisaged for these iodine complexes, among which those with 2-hydroxypropyl-α-cyclodextrin were found the most stable, regardless of the preparation technique. The three prepared cyclodextrin-iodine complexes proved effective as bactericides against S. epidermidis.

Degradation profile of nepafenac in aqueous solution and structural characterization of a novel degradation product.

The stability of the anti-inflammatory drug nepafenac was investigated in aqueous solutions containing hydroxypropyl-ß-cyclodextrin at three different values of pH and degradation products were identified. (2-Amino-3-benzoyl)-oxoacetic acid, previously not reported as nepafenac-related impurity, was isolated and structurally characterized by NMR and ESI-MS analyses. It was also shown that the formation of this α-ketoacid from nepafenac in alkaline water/organic cosolvent solution occurs through an aerobic oxidation of the key intermediate 7-benzoyl-1,3-dihydro-indol-2-one, which in some extent is protected from oxidation in the presence of the cyclodextrin additive.