Dehydrodipeptide Hydrogelators Containing Naproxen N-Capped Tryptophan: Self-Assembly, Hydrogel Characterization, and Evaluation as Potential Drug Nanocarriers.

In this work, we introduce dipeptides containing tryptophan N-capped with the nonsteroidal anti-inflammatory drug naproxen and C-terminal dehydroamino acids, dehydrophenylalanine (ΔPhe), dehydroaminobutyric acid (ΔAbu), and dehydroalanine (ΔAla) as efficacious protease resistant hydrogelators. Optimized conditions for gel formation are reported. Transmission electron microscopy experiments revealed that the hydrogels consist of networks of micro/nanosized fibers formed by peptide self-assembly. Fluorescence and circular dichroism spectroscopy indicate that the self-assembly process is driven by stacking interactions of the aromatic groups. The naphthalene groups of the naproxen moieties are highly organized in the fibers through chiral stacking. Rheological experiments demonstrated that the most hydrophobic peptide (containing C-terminal ΔPhe) formed more elastic gels at lower critical gelation concentrations. This gel revealed irreversible breakup, while the C-terminal ΔAbu and ΔAla gels, although less elastic, exhibited structural recovery and partial healing of the elastic properties. A potential antitumor thieno[3,2-b]pyridine derivative was incorporated (noncovalently) into the gel formed by the hydrogelator containing C-terminal ΔPhe residue. Fluorescence and Förster resonance energy transfer measurements indicate that the drug is located in a hydrophobic environment, near/associated with the peptide fibers, establishing this type of hydrogel as a good drug-nanocarrier candidate.

Enhancing Functionalization of Health Care Textiles with Gold Nanoparticle-Loaded Hydroxyapatite Composites.

Hospitals and nursing home wards are areas prone to the propagation of infections and are of particular concern regarding the spreading of dangerous viruses and multidrug-resistant bacteria (MDRB). MDRB infections comprise approximately 20% of cases in hospitals and nursing homes. Healthcare textiles, such as blankets, are ubiquitous in hospitals and nursing home wards and may be easily shared between patients/users without an adequate pre-cleaning process. Therefore, functionalizing these textiles with antimicrobial properties may considerably reduce the microbial load and prevent the propagation of infections, including MDRB. Blankets are mainly comprised of knitted cotton (CO), polyester (PES), and cotton-polyester (CO-PES). These fabrics were functionalized with novel gold-hydroxyapatite nanoparticles (AuNPs-HAp) that possess antimicrobial properties, due to the presence of the AuNPs' amine and carboxyl groups, and low propensity to display toxicity. For optimal functionalization of the knitted fabrics, two pre-treatments, four different surfactants, and two incorporation processes were evaluated. Furthermore, exhaustion parameters (time and temperature) were subjected to a design of experiments (DoE) optimization. The concentration of AuNPs-HAp in the fabrics and their washing fastness were critical factors assessed through color difference (ΔE). The best performing knitted fabric was half bleached CO, functionalized using a surfactant combination of Imerol® Jet-B (surfactant A) and Luprintol® Emulsifier PE New (surfactant D) through exhaustion at 70 °C for 10 min. This knitted CO displayed antibacterial properties even after 20 washing cycles, showing its potential to be used in comfort textiles within healthcare environments.

Unveiling the Role of Capping Groups in Naphthalene N-Capped Dehydrodipeptide Hydrogels.

Self-assembled peptide-based hydrogels are archetypical nanostructured materials with a plethora of foreseeable applications in nanomedicine and as biomaterials. N-protected di- and tri-peptides are effective minimalist (molecular) hydrogelators. Independent variation of the capping group, peptide sequence and side chain modifications allows a wide chemical space to be explored and hydrogel properties to be tuned. In this work, we report the synthesis of a focused library of dehydrodipeptides N-protected with 1-naphthoyl and 2-naphthylacetyl groups. The 2-naphthylacetyl group was extensively reported for preparation of peptide-based self-assembled hydrogels, whereas the 1-naphthaloyl group was largely overlooked, owing presumably to the lack of a methylene linker between the naphthalene aromatic ring and the peptide backbone. Interestingly, dehydrodipeptides N-capped with the 1-naphthyl moiety afford stronger gels, at lower concentrations, than the 2-naphthylacetyl-capped dehydrodipeptides. Fluorescence and circular dichroism spectroscopy showed that the self-assembly of the dehydrodipeptides is driven by intermolecular aromatic π-π stacking interactions. Molecular dynamics simulations revealed that the 1-naphthoyl group allows higher order aromatic π-π stacking of the peptide molecules than the 2-naphthylacetyl group, together with hydrogen bonding of the peptide scaffold. The nanostructure of the gel networks was studied by TEM and STEM microscopy and was found to correlate well with the elasticity of the gels. This study contributes to understanding the interplay between peptide and capping group structure on the formation of self-assembled low-molecular-weight peptide hydrogels. Moreover, the results presented here add the 1-naphthoyl group to the palette of capping groups available for the preparation of efficacious low-molecular-weight peptide-based hydrogels.

Self-assembled RGD dehydropeptide hydrogels for drug delivery applications.

Peptide-based self-assembled hydrogels have triggered remarkable research interest in recent years owing to their biocompatibility and biomimetic properties and responsiveness, which warrant many technological and biomedical applications. Dehydrodipeptides N-capped with naproxen emerged from our research as effective hydrogelators endowed with resistance to proteolysis. Dehydrodipeptide-based hydrogels are promising nanocarriers for drug delivery applications. In this work, we demonstrate that dehydrodipetide Npx-l-Ala-Z-ΔPhe-OH can be deployed as a minimalist hydrogelator module for synthesizing a gelating construct Npx-l-Ala-Z-ΔPhe-G-R-G-D-G-OH bearing a GRGDG adhesion motif. The self-assembly of the peptide construct and the drug delivery properties of the hydrogel were studied in this work. The peptide construct showed no toxicity towards a fibroblast cell line expressing the αvß3 integrin. Docking studies suggest that the hydrogelator block does not interfere with the recognition of the RGD motif by the integrin receptor. The self-assembly seems to be directed by intermolecular naphthalene π-π stacking interactions, with the peptide backbone assuming a random coil conformation both in solution and in the gel phase. TEM and STEM imaging revealed that the hydrogel is made of entangled bundles of long thin fibres (width circa 23 nm). The hydrogel exhibits viscoelastic properties, thermo-reversibility and recovery after mechanical fluidization. FRET studies showed that curcumin incorporated into the hydrogel interacts non-covalently with the hydrogel fibrils. Delivery of curcumin from the hydrogel into Nile red loaded model membranes (SUVs) was demonstrated by FRET. Naproxen N-capped dehydrodipeptides are efficacious minimalist hydrogelator modules for obtaining hydrogels functionalized with peptide ligands for cell receptors. These hydrogels are potential nanocarriers for drug delivery.

Cerebral gas embolism associated with central venous catheter: Systematic review.

OBJECTIVE: Cerebral gas embolism (CGE) is a potentially catastrophic complication of central venous catheters (CVCs) manipulation or accidental disconnection, which is rarely reported in the literature. This systematic review aims to characterize the clinical manifestations, imaging features and outcome of CGE associated with CVCs. METHODS: Systematic literature search of all published cases of CGE associated with CVCs, and identification of previously unreported local cases. Descriptive analysis of all cases, mortality analysis for cases with individualized data. RESULTS: Of the 158 patients with CGE associated with CVCs found, 71.8% were male and mean age was 56.4years. CGE symptoms frequently occurred while in the upright position. The most frequent neurological manifestation was sudden-onset focal neurological sign (67.7%), followed by coma (59.5%), epileptic seizures (24.7%) and encephalopathy (21.5%). Imaging revealed intracranial air bubbles in 69.1% and cerebral ischemia or edema was demonstrated in 66.7%. Overall mortality was 21.7%, and clinical predictors of mortality were increasing age (p<0.001), coma (p=0.001), cardiorespiratory arrest shortly after symptom onset (p<0.001) and male sex (p=0.035). CONCLUSIONS: CGE associated with CVCs may mimic ischemic stroke, but patients frequently present a severe vigilance disturbance and epileptic seizures. Mortality occurs in 1/5 of patients, which substantiates implementation of protocols and measures to prevent this severe complication of CVC use.