Contact Lenses Delivering Nitric Oxide under Daylight for Reduction of Bacterial Contamination

Ocular infection due to microbial contamination is one of the main risks associated with the wearing of contact lens, which demands novel straightforward strategies to find reliable solutions. This contribution reports the preparation, characterization and biological evaluation of soft contact lenses (CL) releasing nitric oxide (NO), as an unconventional antibacterial agent, under daylight exposure. A tailored NO photodonor (NOPD) was embedded into commercial CL leading to doped CL with an excellent optical transparency (transmittance = 100%) at λ ≥ 450 nm. The NOPD results homogeneously distributed in the CL matrix where it fully preserves the photobehavior exhibited in solution. In particular, NO release from the CL and its diffusion in the supernatant physiological solution is observed upon visible light illumination. The presence of a blue fluorescent reporting functionality into the molecular skeleton of the NOPD, which activates concomitantly to the NO photorelease, allows the easy monitoring of the NO delivery in real-time and confirms that the doped CL work under daylight exposure. The NO photoreleasing CL are well-tolerated in both dark and light conditions by corneal cells while being able to induce good growth inhibition of Staphylococcus aureus under visible light irradiation. These results may pave the way to further engineering of the CL with NOPD as innovative ocular devices activatable by sunlight

The Digestibility of Hibiscus sabdariffa L. Polyphenols Using an In Vitro Human Digestion Model and Evaluation of Their Antimicrobial Activity

Hibiscus sabdariffa L. (H.s.) is a polyphenolic-rich plant commonly consumed either as a beverage or spice. The aim of the present study was to evaluate the in vitro digestibility of H.s. polyphenols using an in vitro model of digestion which simulates the human stomach and small intestine. The bioaccessible polyphenols released in the digested samples were analyzed by liquid chromatography coupled to photodiode array and mass spectrometry detection. H.s. anthocyanins (cyanidin-3-O-sambubioside and delphinidin-3-O-sambubioside) content drastically dropped during the digestion process from 2.91 ± 0.03 µg g−1 and 8.53 ± 0.08 µg g−1 (w/w) CG (Cyanidin-glucoside) in the raw extract, respectively, to 0.12 ± 0.01 µg g−1 0.12 ± 0.01 µg g−1 (w/w) CG at the end of duodenal digestion. Total polyphenols also have shown a decrease from 1192.65 ± 30.37 µg g−1 (w/w) in the raw extract to 282.24 ± 7.21 µg g−1 (w/w) by the end of gastric digestion, in contrast to their increase by the end of duodenal digestion 372.91 ± 3.97 µg g−1 (w/w). On the other hand, the decrease in certain compounds (e.g., caffeoylquinicandcoumaroylquinic acids) was observed during gastric digestion resulting in an increase of quinic acid in the duodenal aliquots, thus suggesting that this compound was derived from the degradation of the more complex hydroxycinnamic acids. H.s. extract also exhibited a bacteriostatic effect against Staphylococcus aureus ATCC 6538 (MIC of 2.5 mg mL−1) and a bactericidal effect against a food isolate of Listeria monocytogenes (MBC of 2.5 mg mL−1). The undigested polyphenols of H.s. in the upper gastrointestinal tract enters the colon, where they are metabolized by the gut microbiota. The present study results showed that resistance of H.s. polyphenols during gastrointestinal digestion might affect their uptake, resulting in a decrease in their digestibility

Studio dell’attività in vitro e in vivo dell’associazione clotrimazolometronidazolo: attività antimicotica e antibatterica in vitro ed efficacia nella terapia delle vaginiti/vaginosi

Nel presente studio la valutazione dell’efficacia microbiologica e clinica di una associazione metronidazolo + clotrimazolo (in rapporto quantitativo di 5:1) nella terapia topica di vaginiti miste (candidosi/vaginosi) è stata comparata con il grado di interferenza che tale chemioterapico può determinare sul mantenimento/ripristino del microbiota lattobacillare. Sono state studiate 20 donne con diagnosi clinica, microbiologicamente confermata, di vulvovaginite micotica e/o vaginosi. L’attività antimicrobica di clotrimazolo e metronidazolo è stata studiata su ceppi d’isolamento e di collezione. Entrambi i chemioterapici sono stati valutati singolarmente ed in associazione. Il clotrimazolo si è mostrato attivo nei confronti dei miceti saggiati sia da soli che in associazione con il metronidazolo. Come atteso, l’associazione delle due sostanze non migliora l’attività intrinseca del clotrimazolo. Sia clotrimazolo che metronidazolo sono risultati inattivi nei confronti di batteri Gram-positivi e Gram-negativi aerobi; al contrario entrambi erano attivi nei confronti di G. vaginalis. In tutte le pazienti studiate è stata riscontrata l’assenza di crescita dei patogeni isolati, sia alla prima visita dopo terapia, sia al followup. Il grado lattobacillare è ritornato normale a 30 giorni dalla fine della terapia. Non sono stati riportati casi di recidiva

Efficacy of carvacrol against resistant rapidly growing mycobacteria in the planktonic and biofilm growth mode.

Rapidly growing mycobacteria (RGM) are environmental bacteria found worldwide with a propensity to produce skin and soft-tissue infections. Among them, the most clinically relevant species is Mycobacterium abscessus. Multiple resistance to antibiotics and the ability to form biofilm contributes considerably to the treatment failure. The search of novel anti-mycobacterial agents for the control of biofilm growth mode is crucial. The aim of the present study was to evaluate the activity of carvacrol (CAR) against planktonic and biofilm cells of resistant RGM strains. The susceptibility of RGM strains (n = 11) to antibiotics and CAR was assessed by MIC/MBC evaluation. The CAR activity was estimated by also vapour contact assay. The effect on biofilm formation and preformed biofilm was measured by evaluation of bacterial growth, biofilm biomass and biofilm metabolic activity. MIC values were equal to 64 μg/mL for most of RGM isolates (32-512 μg/mL), MBCs were 2-4 times higher than MICs, and MICs of vapours were lower (16 μg/mL for most RGM isolates) than MICs in liquid phase. Regarding the biofilm, CAR at concentrations of 1/2 × MIC and 1/4 × MIC showed a strong inhibition of biofilm formation (61-77%) and at concentration above the MIC (2-8 × MIC) produced significant inhibition of 4- and 8-day preformed biofilms. In conclusion, CAR could have a potential use, also in vapour phase, for the control of RGM

A thermoresponsive gel photoreleasing nitric oxide for potential ocular applications

We report herein the design, preparation, characterization and biological evaluation of a thermoresponsive gel based on binary mixtures of Pluronics co-polymers F127 and P123, the latter being covalently functionalized with a nitric oxide (NO) photodonor (NOPD). The weight ratio between the two polymeric components is optimized in order to observe gelation of their saline water solution in the range of 32–35 1C, in order to exploit the therapeutic properties of NO for potential ocular applications. Rheological measurements were performed to evaluate the gelation temperature and, hence, to select a co-polymer mixture specifically appropriate for the reference application. Integration of the NOPD into the polymeric scaffold does not affect its rheological and spectroscopic properties, making it a good absorber of visible light both in solution and in the gel phase. Irradiation of the saline solution of the polymeric components with visible light triggers NO release, which occurs with an efficiency of more than one order of magnitude faster than that observed for the isolated NOPD. The polymeric system fully preserves such photobehavior after gelation as demonstrated by the effective NO photorelease from the gel matrix and its diffusion in the supernatant upon illumination. The gel is well-tolerated in both dark and light conditions by corneal cells, while being able to induce growth inhibition towards Staphylococcus aureus under visible light irradiation and has high moduli which can contribute to an adequate retention time within the eyes