Wound Dressing: Combination of Acacia Gum/PVP/Cyclic Dextrin in Bioadhesive Patches Loaded with Grape Seed Extract.

The success of wound treatment is conditioned by the combination of both suitable active ingredients and formulation. Grape seed extract (GSE), a waste by-product obtained by grape processing, is a natural source rich in many phenolic compounds responsible for antioxidant, anti-inflammatory, and antimicrobial activities and for this reason useful to be used in a wound care product. Bioadhesive polymeric patches have been realized by combining acacia gum (AG) and polyvinylpyrrolidone (PVP). Prototypes were prepared by considering different AG/PVP ratios and the most suitable in terms of mechanical and bioadhesion properties resulted in the 9.5/1.0 ratio. This patch was loaded with GSE combined with cyclic dextrin (CD) to obtain the molecular dispersion of the active ingredient in the dried formulation. The loaded patch resulted mechanically resistant and able to release GSE by a sustained mechanism reaching concentrations able to stimulate keratinocytes' growth, to exert both antibacterial and antioxidant activities.

Emulgel Loaded with Flaxseed Extracts as New Therapeutic Approach in Wound Treatment.

Dry (D.E.) and liquid (L.E.) extracts were prepared from flaxseeds and their application in health field was evaluated. The chemical analysis showed that D.E. is rich in the lignan secoisolariciresinol diglucoside and L.E. in unsaturated triglycerides containing linolenic acid. Mainly, D.E. showed reducing (15.73 µmol Fe2+/g) and radical scavenging capacities (5.25 mg TE/g) and ability to down-regulate the expression of the pro-inflammatory cytokines NO (IC50 = 0.136 ± 0.009 mg/mL) and IL-6 (IC50 = 0.308 ± 0.103 mg/mL), suggesting its use in wound treatment. D.E. and L.E. were active against S. pyogenes and D.E. also against S. aureus. The two extracts were combined in a novel O/W emulgel in which the water phase was viscosized using a low molecular weight and highly deacetylated chitosan (1% wt./v). The presence of this polymer in the emulgel decreased the MIC values of the extracts. In fact, MIC shifted from 0.59 mg/mL to 0.052 mg/mL for D.E. and from 0.22 mg/mL to 0.036 mg/mL for L.E., concentrations safe both for keratinocytes and macrophages. Moreover, the emulgel demonstrated to inhibit S. aureus, P. aeruginosa, S. pyogenes, E. coli, and K. pneumoniae growth (inhibition halos 24-36 mm), strains often responsible for diabetic foot ulcer infection.

Development and Characterization of Xanthan Gum and Alginate Based Bioadhesive Film for Pycnogenol Topical Use in Wound Treatment.

Pycnogenol (PYC) is a concentrate of phenolic compounds derived from French maritime pine; its biological activity as antioxidant, anti-inflammatory and antibacterial suggests its use in the treatment of open wounds. A bioadhesive film, loaded with PYC, was prepared by casting, starting with a combination of two biopolymer acqueous solutions: xanthan gum (1% wt/wt) and sodium alginate (1.5% wt/wt), in a 2.5/7.5 (wt/wt) ratio. In both solutions, glycerol (10% wt/wt) was added as plasticizing agent. The film resulted in an adhesive capable to absorb a simulated wound fluid (~ 65% wt/wt within 1 h), therefore suitable for exuding wounds. The mechanical characterization showed that the film is deformable (elastic modulus E = 3.070 ± 0.044 MPa), suggesting adaptability to any type of surface and resistance to mechanical solicitations. PYC is released within 24 h by a sustained mechanism, achieving a maximum concentration of ~ 0.2 mg/mL, that is safe for keratinocytes, as shown by cytotoxicity studies. A concentration of 0.015 mg/mL is reached in the first 5 min after application, at which point PYC stimulates keratinocyte growth. These preliminary results suggest the use of PYC in formulations designed for topical use.

Integrating experimental and computational techniques to study chromatographic enantioresolutions of chiral tetrahydroindazole derivatives.

With the selection of partially saturated 2H-indazoles as model compounds, we demonstrate the possibility to use Whelk-O1 chiral stationary phases (CSPs) to succeed in efficient small-scale preparative enantioseparations. Runs of three consecutive liquid chromatography injections (about 300 µg of racemate repeatedly injected in a 100 µL loop) produced groups of peaks without band contamination (α = 1.2 and RS = 2.57). With this procedure approximately 3.0 mg of each enantiomer, with enantiomeric excess ≥ 97% were obtained. Very profitably, the high volatility of n-hexane used as the sole eluent facilitated the solvent evaporation after the enantiomer recovery. High resolution mass spectrometry analysis confirmed that the chemical identity of the two enantiomers was preserved along the entire process. The ability of Whelk-O1 phases in enantioseparating structurally similar compounds was confirmed with the analysis of other two racemates. Moreover, the relevant chemoselectivity exhibited by the CSP towards the three racemates should allow to simultaneously optimizing the enantioselectivity of different analytes and perform small-scale enantioresolutions of different compounds during the same run. In this study, the integration of experimental off-line electronic circular dichroism analysis with ab initio time-dependent density-functional theory simulations facilitated the assignment of the absolute configuration of the single enantiomers, while a molecular dynamics protocol can be useful to make a priori predictions of the enantioseparation ability of CSP towards selected compounds.

Binding properties of different categories of IDO1 inhibitors: a microscale thermophoresis study.

AIM: Inhibition of IDO1 is a strategy pursued in the immune-oncology pipeline for the development of novel anticancer therapies. At odds with an ever-increasing number of inhibitors being disclosed in the literature and patent applications, only very few compounds have hitherto advanced in clinical settings. MATERIALS & METHODS: We have used MicroScale Thermophoresis analysis and docking calculations to assess on a quantitative basis the binding properties of distinct categories of inhibitors to IDO1. RESULTS: Results shed further light on hidden molecular aspects governing the recognition by the enzyme of compounds with different mechanism of inhibition. CONCLUSION: Results pinpoint specific binding features of distinct inhibitors to IDO1 that offer clues for the design of next-generation inhibitors of the enzyme.