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Granata G.,National Research Council Italy | Paterniti I.,Messina University | Geraci C.,National Research Council Italy | Cunsolo F.,National Research Council Italy | And 5 more authors.
Molecular Pharmaceutics | Year: 2017

Curcumin is an Indian spice with a wide spectrum of biological and pharmacological activities but poor aqueous solubility, rapid degradation, and low bioavailability that affect medical benefits. To overcome these limits in ophthalmic application, curcumin was entrapped in a polycationic calix[4]arene-based nanoaggregate by a simple and reproducible method. The calix[4]arene-curcumin supramolecular assembly (Calix-Cur) appeared as a clear colloidal solution consisting in micellar nanoaggregates with size, polydispersity index, surface potential, and drug loading percentage meeting the requirements for an ocular drug delivery system. The encapsulation in the calix[4]arene nanoassembly markedly enhanced the solubility, reduced the degradation, and improved the anti-inflammatory effects of curcumin compared to free curcumin in both in vitro and in vivo experiments. Calix-Cur did not compromise the viability of J774A.1 macrophages and suppressed pro-inflammatory marker expression in J774A.1 macrophages subjected to LPS-induced oxidative stress. Histological and immunohistochemical analyses showed that Calix-Cur reduced signs of inflammation in a rat model of LPS-induced uveitis when topically administrated in the eyes. Overall, the results supported the calix[4]arene nanoassembly as a promising nanocarrier for delivering curcumin to anterior ocular tissues. © 2017 American Chemical Society.


Faraldi F.,Presidio | Papa V.,SIFI SpA | Santoro D.,SIFI SpA | Rasa D.,SIFI SpA | And 3 more authors.
Clinical Ophthalmology | Year: 2012

Purpose: The aim of this study was to investigate the effects of an ophthalmic gel containing sodium hyaluronate and xanthan gum in addition to the antibiotic netilmicin in the management of traumatic corneal abrasions. Patients and methods: Patients with traumatic corneal abrasions were randomly treated as follows: Group A (n = 20) with an occlusive patching for 12 hours plus one drop of an eye gel containing 0.15% sodium hyaluronate, 1% xanthan gum and 0.3% netilmicin qid for 5 days; and Group B (n = 20) with an occlusive patching for 2-3 days plus one application of 0.3% netilmicin ophthalmic ointment qid for 5 days. All patients were evaluated after the third and seventh day by slit-lamp examination, fluorescein staining, and corneal defect photograph in order to assess corneal re-epithelialization. Conjunctival hyperaemia, lid oedema, subjective symptoms of discomfort, and conjunctival swabs were also evaluated. Results: No statistically significant difference was observed between the groups in terms of the extent of corneal healing after 3 days of treatment. Both treatments were also highly effective in decreasing the erosion score and the conjunctival hyperemia(P < 0.0001, P < 0.005, respectively) without any significant difference between the two types of treatment. Subjective symptoms of discomfort and conjunctival swabs were also evaluated. Conclusion: In the management of traumatic corneal abrasions, the administration of an eye gel containing sodium hyaluronate and xanthan gum is able to reduce the length of occlusive patching. In addition, the presence of netilmicin guarantees good antibiotic prophylaxis during the wound repair process. © 2012 Faraldi et al, publisher and licensee Dove Medical Press Ltd.


Zammataro A.,SIFI SpA | Civiale C.,SIFI SpA | Saletti R.,University of Catania | Foti S.,University of Catania
Journal of Mass Spectrometry | Year: 2011

A rapid, selective and sensitive method for quantification of latanoprost free acid in rabbit aqueous humor (AH) and ciliary body (CB) using reverse phase-high performance liquid chromatography coupled with electrospray ionization (ESI)-mass spectrometry/mass spectrometry has been developed and validated. Quantification in AH and CB was achieved by stable isotope dilution employing tetra-deuterated analog of latanoprost free acid, used as internal standard. Sample preparation was based on protein precipitation with methanol in AH, and on liquid extraction with a mixture of ethyl acetate and isopropanol 60:40 (v/v) in CB. Elution was achieved on an octylsilica (C8) column, using an isocratic elution method. Detection was performed on a triple quadrupole mass spectrometer, using ESI in positive ion selected reaction monitoring mode. Calibration curves were linear in the validated concentration ranges of 10-160 ng/mL in AH and 80-1280 ng/g in CB. The accuracy and precision values, obtained from three different sets of quality control samples, each analyzed in triplicate on three different days, were within the generally accepted criteria for analytical methods (< 15%). The limit of detection was 30.66 pg/mL in AH and 237.75 pg/g in CB. The assay proved to be accurate and precise when applied to the in vivo study of latanoprost free acid in rabbit AH and CB after single administration of an eye drops containing latanoprost. Copyright © 2011 John Wiley & Sons, Ltd.


Zammataro A.,SIFI SpA | Saletti R.,University of Catania | Civiale C.,SIFI SpA | Muccilli V.,University of Catania | And 2 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2010

A rapid, sensitive and selective method for the simultaneous quantification of carteolol and dorzolamide in rabbit aqueous humor (AH) and ciliary body (CB) has been developed and validated using reversed phase-high performance liquid chromatography (RP-HPLC) with isocratic elution coupled with atmospheric pressure chemical ionization mass spectrometry/mass spectrometry (APCI-MS/MS). The analytes and nadolol (used as internal standard, IS) were purified from AH by protein precipitation. The sample preparation from CB was based on a two steps extraction procedure at different pH, utilizing a liquid-liquid extraction with a mixture of ethyl acetate, toluene and isopropanol 50:40:10 (v/v) at pH 8, followed by a second extraction with ethyl acetate at pH 11. The combined organic extracts were then back extracted into 0.1% aqueous trifluoroacetic acid (TFA). The accuracy and precision values, calculated from three different sets of quality control samples analyzed in sestuplicate on three different days, were within the generally accepted criteria for analytical methods (<15%). The assay proved to be accurate and precise when applied to the in vivo study of carteolol and dorzolamide in rabbit AH and CB after single administration of an eye drops containing both drugs. © 2010 Elsevier B.V. All rights reserved.


Marino N.,Laboratory of Photochemistry | Perez-Lloret M.,Laboratory of Photochemistry | Blanco A.R.,SIFI S.p.A. | Venuta A.,University of Naples Federico II | And 2 more authors.
Journal of Materials Chemistry B | Year: 2016

A novel photoresponsive molecular hybrid has been embedded in poly(lactic-co-glycolic acid) (PLGA) to give an antibacterial polymeric film generating nitric oxide (NO) under visible light, with concomitant fluorescence reporting of NO release. The molecular hybrid integrates a nitroaniline NO photodonor and a coumarin latent fluorophore in the same molecular skeleton and results in quite homogeneous distribution in the polymer matrix where it preserves well the photobehavior exhibited in solution. The doped PLGA film shows an excellent optical transparency and can be excited by visible light leading to the production of NO and the parallel fluorescence revival of the coumarin fluorophore, which acts as an optical NO reporter. Photogenerated NO diffuses out of the polymer film, can be transferred to a biological milieu and induces remarkable antibacterial activity against Escherichia coli. © The Royal Society of Chemistry 2016.


Di Bari I.,Laboratory of Photochemistry | Picciotto R.,Laboratory of Photochemistry | Granata G.,CNR Institute of Biomolecular Chemistry | Blanco A.R.,SIFI S.p.A. | And 2 more authors.
Organic and Biomolecular Chemistry | Year: 2016

A hydrophobic N-dodecyl-3-(trifluoromethyl)-4-nitrobenzenamine has been synthesized as a suitable NO photodonor and encapsulated in a nanocontainer based on a polycationic calix[4]arene derivative, leading to a supramolecular micellar-like nanoassembly ca. 45 nm in diameter. Visible light excitation of this nanoconstruct triggers NO generation with an efficiency remarkably higher than that observed for the free NO photoreleaser. This amplified NO release results in considerable antibacterial activity against Staphylococcus aureus (ATCC 6538) and Pseudomonas aeruginosa (ATCC 9027) as representative Gram positive and Gram negative bacteria, respectively. © 2016 The Royal Society of Chemistry.


McCann L.C.,Glasgow Caledonian University | Tomlinson A.,Glasgow Caledonian University | Pearce E.I.,Glasgow Caledonian University | Papa V.,SIFI SpA
Cornea | Year: 2012

Purpose: To compare the efficacies of sodium hyaluronate, hydroxypropyl methylcellulose (HPMC), and a new oil-in-water emulsion (Emustil unidose; SIFI) in the management of lipiddeficient dry eye.Methods: Seventy-five subjects with dry eye were randomly divided into 3 groups. Each was allocated sodium hyaluronate, HPMC, or emulsion eyedrops to be used four times daily for 90 days. Parameters were measured at baseline, 30 days, and 90 days. A compliance visit was performed at days 7 and 60.Results: Significant reduction (P < 0.05) in evaporation and improvement in symptoms in all groups were found. No statistically significant increase in tear turnover rate (TTR) was found with any solution. A significant difference in tear stability and noninvasive tear break-up time (NITBUT) was found in the emulsion and sodium hyaluronate groups but not in the HPMC group (P > 0.05). There was a significant decrease in osmolarity and corneal staining in the emulsion group (P< 0.001) but not in the sodium hyaluronate or HPMC group (P > 0.05).Conclusions: A significant reduction in evaporation and improvement in symptoms in all therapy groups were found from baseline to 90 days. However, no significant effect was seen on TTR for any group. The emulsion drops were shown to perform best, improving tear stability, and decreasing osmolarity and corneal staining. These results are consistent with improvements in the lipid layer of the tear film as a result of prolonged use of emulsion drops. Copyright © 2011 by Lippincott Williams & Wilkins.


The present invention relates to the use of xanthan gum as re-epithelializing agent and, in particular, to a pharmaceutical formulation comprising xanthan gum as a re-epithelializing active principle eventually mixed with hyaluronic acid. Said use and composition speed up and improve advantageously the formation of newly grown epithelium.


Spatafora C.,University of Catania | Daquino C.,SIFI S.p.A. | Tringali C.,University of Catania | Amorati R.,University of Bologna
Organic and Biomolecular Chemistry | Year: 2013

Benzo[kl]xanthene lignans, promising bioactive polyphenols obtained by biomimetic oxidative coupling of caffeic acid derivatives, react efficiently with peroxyl radicals in both polar and non-polar solvents, thanks to the simultaneous presence of guaiacol-like and catechol-like OH-groups. This journal is © The Royal Society of Chemistry 2013.


A rapid, selective and sensitive method for quantification of latanoprost free acid in rabbit aqueous humor (AH) and ciliary body (CB) using reverse phase-high performance liquid chromatography coupled with electrospray ionization (ESI)-mass spectrometry/mass spectrometry has been developed and validated. Quantification in AH and CB was achieved by stable isotope dilution employing tetra-deuterated analog of latanoprost free acid, used as internal standard. Sample preparation was based on protein precipitation with methanol in AH, and on liquid extraction with a mixture of ethyl acetate and isopropanol 60:40 (v/v) in CB. Elution was achieved on an octylsilica (C8) column, using an isocratic elution method. Detection was performed on a triple quadrupole mass spectrometer, using ESI in positive ion selected reaction monitoring mode. Calibration curves were linear in the validated concentration ranges of 10-160 ng/mL in AH and 80-1280 ng/g in CB. The accuracy and precision values, obtained from three different sets of quality control samples, each analyzed in triplicate on three different days, were within the generally accepted criteria for analytical methods (< 15%). The limit of detection was 30.66 pg/mL in AH and 237.75 pg/g in CB. The assay proved to be accurate and precise when applied to the in vivo study of latanoprost free acid in rabbit AH and CB after single administration of an eye drops containing latanoprost.

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