Design and Fabrication of Polyvinylpyrrolidone-based Intelligent Materials Suitable for Controlled Release and Wound Treatment

Polyvinylpyrrolidone (PVP) is probably one of the most utilized pharmaceutical polymers with applications ranging from blood plasma substitute to nanoparticle drug delivery since its synthesis in 1938. It is a highly biocompatible, non-toxic and transparent film-forming polymer. Although high solubility of PVP in an aqueous environment is advantageous, it still poses several problems for some applications in which sustained targeting and release are needed, or hydrophobic drug inclusion and delivery systems are to be designed. For this reason, in the field of controlled drug release, it is often used as an additive and not as a protagonist. On the other hand, in case of wound treatment, PVP can be a suitable biopolymer for the design of wound dressings due to its capacity to inhibit the crystallinity of several drugs, opening to their topical application, and its adhesive properties to the skin. Therefore, the main goal of this Ph.D. was to demonstrate that this underestimated synthetic polymer can be a proper based material for the design, the fabrication and the formulation of new smart wound dressings for the delivery of antibiotic and antioxidant compounds. In the first part of this Ph.D. study, PVP and acetic acid (AcOH) were used to inhibit the crystallization of the antibiotic Ciprofloxacin (Cipro) and to prepare transparent PVP foils as well as nanofiber mats. The presence of the antibiotic and the acid inside of the PVP matrix caused a plasticizer effect of these ingredients in the final mechanical properties of the films. Both films and nanofibers were able to release the Cipro, and an antibacterial synergism between acetic acid and the antibiotic were highlighted in vitro antibacterial assay. The PVP/Cipro/AcOH materials showed biocompatibility and a different rate of resorption in an in vivo wound mice model. In the second part of the Ph.D., a multifunctional polyvinylpyrrolidone/hyaluronic acid-based bilayer construct for sequential delivery of cutaneous antiseptic and antibiotic was designed and fabricated by using two scalable methodologies. The bilayer material showed strong adhesion to skin, effective antibacterial activity against three strains, biocompatibility, hemocompatibility, anti-inflammatory properties both in vitro and in vivo, resorption by the skin and accelerate the wound closure in mice model. Then, the PVP/Cipro/AcOH films and nanofibers were further characterized on an infected wound model based on ex-vivo human skin. The materials resulted non-toxic and with suitable profiles of the release of Cipro inside of the skin. Moreover, they highlighted a strong antibacterial activity against biofilms infection of Pseudomonas aeruginosa and, especially, in case of the films they were able to eradicate completely the biofilms from the skin. Finally, PVP was combined with the dietary phenolic compounds, p-coumaric acid (PCA). The introduction of the PCA in transparent films led to an increase of the hydrophobicity of the PVP-based matrix. Indeed, changes in water contact angles, water uptake and the rate of dissolution in water were found. Furthermore, the new biocomposites were investigated as drug delivery system of two model drugs and their antioxidant and anti-inflammatory activity were analyzed in vitro and in vivo, respectively. In conclusions, several PVP-based wound dressings were designed and fabricated, demonstrating their potential efficacy for the treatment of infected wounds, burns, and chronic wounds

Evaluation of Drug Delivery and Efficacy of Ciprofloxacin-Loaded Povidone Foils and Nanofiber Mats in a Wound-Infection Model Based on Ex Vivo Human Skin

Topical treatment of wound infections is often a challenge due to limited drug availability at the site of infection. Topical drug delivery is an attractive option for reducing systemic side effects, provided that a more selective and sustained local drug delivery is achieved. In this study, a poorly water-soluble antibiotic, ciprofloxacin, was loaded on polyvinylpyrrolidone (PVP)-based foils and nanofiber mats using acetic acid as a solubilizer. Drug delivery kinetics, local toxicity, and antimicrobial activity were tested on an ex vivo wound model based on full-thickness human skin. Wounds of 5 mm in diameter were created on 1.5 × 1.5 cm skin blocks and treated with the investigated materials. While nanofiber mats reached the highest amount of delivered drug after 6 h, foils rapidly achieved a maximum drug concentration and maintained it over 24 h. The treatment had no effect on the overall skin metabolic activity but influenced the wound healing process, as observed using histological analysis. Both delivery systems were efficient in preventing the growth of Pseudomonas aeruginosa biofilms in ex vivo human skin. Interestingly, foils loaded with 500 µg of ciprofloxacin accomplished the complete eradication of biofilm infections with 1 × 109 bacteria/wound. We conclude that antimicrobial-loaded resorbable PVP foils and nanofiber mats are promising delivery systems for the prevention or topical treatment of infected wounds

Data concerning the proteolytic resistance and oxidative stress in LAN5 cells after treatment with BSA hydrogels

AbstractProteolytic resistance is a relevant aspect to be tested in the formulation of new nanoscale biomaterials. The action of proteolytic enzymes is a very fast process occurring in the range of few minutes. Here, we report data concerning the proteolytic resistance of a heat-set BSA hydrogel obtained after 20-hour incubation at 60°C prepared at the pH value of 3.9, pH at which the hydrogel presents the highest elastic character with respect to gel formed at pH 5.9 and 7.4 “Heat-and pH-induced BSA conformational changes, hydrogel formation and application as 3D cell scaffold” (G. Navarra, C. Peres, M. Contardi, P. Picone, P.L. San Biagio, M. Di Carlo, D. Giacomazza, V. Militello, 2016) [1]. We show that the BSA hydrogel produced by heating treatment is protected by the action of proteinase K enzyme. Moreover, we show that LAN5 cells cultured in presence of BSA hydrogels formed at pH 3.9, 5.9 and 7.4 did not exhibit any oxidative stress, one of the first and crucial events causing cell death “Are oxidative stress and mitochondrial dysfunction the key players in the neurodegenerative diseases?” (M. Di Carlo, D. Giacomazza, P. Picone, D. Nuzzo, P.L. San Biagio, 2012) [2] “Effect of zinc oxide nanomaterials induced oxidative stress on the p53 pathway” (M.I. Setyawati, C.Y. Tay, D.T. Leaong, 2013) [3]

Preliminary Validation of the Italian Night Eating Questionnaire (I-NEQ-16): Item Analysis and Factor Structure

Night eating syndrome (NES) severity is usually assessed with the Night Eating Questionnaire (NEQ). Although the most common version of the NEQ is composed of 14 items (NEQ-14), two additional items measuring distress associated with the night eating have been proposed, but they have never been included in past psychometric studies. The aim of the present study was to create an Italian version of the NEQ-16 (I-NEQ-16), with the inclusion of the proposed items for assessing the distress associated with night eating. A major objective of the study was to propose a unidimensional version of the I-NEQ-16 and investigate its psychometric properties. 482 Italian adults (380 women and 102 men; mean age = 25.5, SD = 10.9 years old) were administered the Italian versions of the NEQ, the Night Eating Diagnostic Questionnaire (NEDQ), and questionnaires measuring binge eating, emotional and external eating, diurnal chronotype, insomnia, and anxiety and depression severity. In order to improve the unidimensionality of the I-NEQ-16, we removed from further analyses items 1, 4, and 7, because they increased the heterogeneity of the measure. Confirmatory factor analysis, indicated the fit of a modified one-factor model, allowing correlated errors between three pairs of items. I-NEQ-16 scores were significantly associated with all concurrent questionnaire scores and were able to categorize individuals according to their diagnosis of NES according to the NEDQ. Thus, the I-NEQ-16 is a valid measure that is potentially useful for investigating correlates of night eating in the general population

Mycelium-based biomaterials as smart devices for skin wound healing

Introduction: Recently, mycelia of Ganoderma lucidum and Pleurotus ostreatus, edible fungi, have been characterized in vitro as self-growing biomaterials for tissue engineering since they are constituted of interconnected fibrous networks resembling the dermal collagen structure.Aim: This work aims to investigate the biopharmaceutical properties of G. lucidum and P. ostreatus mycelia to prove their safety and effectiveness in tissue engineering as dermal substitutes.Methods: The mycelial materials were characterized using a multidisciplinary approach, including physicochemical properties (morphology, thermal behavior, surface charge, and isoelectric point). Moreover, preclinical properties such as gene expression and in vitro wound healing assay have been evaluated using fibroblasts. Finally, these naturally-grown substrates were applied in vivo using a murine burn/excisional wound model.Conclusions: Both G. lucidum and P. ostreatus mycelia are biocompatible and able to safely and effectively enhance tissue repair in vivo in our preclinical model

Targets for cancer therapy in childhood sarcomas

Development of chemotherapeutic treatment modalities resulted in a dramatic increase in the survival of children with many types of cancer. Still, in case of some pediatric cancer entities including rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma, survival of patients remains dismal and novel treatment approaches are urgently needed. Therefore, based on the concept of targeted therapy, numerous potential targets for the treatment of these cancers have been evaluated pre-clinically or in some cases even clinically during the last decade. This review gives an overview over many different potential therapeutic targets for treatment of these childhood sarcomas, including receptor tyrosine kinases, intracellular signaling molecules, cell cycle and apoptosis regulators, proteasome, hsp90, histone deacetylases, angiogenesis regulators and sarcoma specific fusion proteins. The large number of potential therapeutic targets suggests that improved comparability of pre-clinical models might be necessary to prioritize the most effective ones for future clinical trials

Colorimetric Indicators Based on Anthocyanin Polymer Composites: A Review

This review explores the colorimetric indicators based on anthocyanin polymer composites fabricated in the last decade, in order to provide a comprehensive overview of their morphological and compositional characteristics and their efficacy in their various application fields. Notably, the structural properties of the developed materials and the effect on their performance will be thoroughly and critically discussed in order to highlight their important role. Finally, yet importantly, the current challenges and the future perspectives of the use of anthocyanins as components of colorimetric indicator platforms will be highlighted, in order to stimulate the exploration of new anthocyanin sources and the in-depth investigation of all the possibilities that they can offer. This can pave the way for the development of high-end materials and the expansion of their use to new application fields

Functional Polymeric Membranes with Antioxidant Properties for the Colorimetric Detection of Amines

Herein, the ability of highly porous colorimetric indicators to sense volatile and biogenic amine vapors in real time is presented. Curcumin-loaded polycaprolactone porous fiber mats are exposed to various concentrations of off-flavor compounds such as the volatile amine trimethylamine, and the biogenic amines cadaverine, putrescine, spermidine, and histamine, in order to investigate their colorimetric response. CIELAB color space analysis demonstrates that the porous fiber mats can detect the amine vapors, showing a distinct color change in the presence of down to 2.1 ppm of trimethylamine and ca. 11.0 ppm of biogenic amines, surpassing the limit of visual perception in just a few seconds. Moreover, the color changes are reversible either spontaneously, in the case of the volatile amines, or in an assisted way, through interactions with an acidic environment, in the case of the biogenic amines, enabling the use of the same indicator several times. Finally, yet importantly, the strong antioxidant activity of the curcumin-loaded fibers is successfully demonstrated through DPPH● and ABTS● radical scavenging assays. Through such a detailed study, we prove that the developed porous mats can be successfully established as a reusable smart system in applications where the rapid detection of alkaline vapors and/or the antioxidant activity are essential, such as food packaging, biomedicine, and environmental protection

Assessment of Affect Lability: Psychometric Properties of the ALS-18

Affect lability, an important aspect of emotion dysregulation, characterizes several psychiatric conditions. The short Affective Lability Scales (ALS-18) measures three aspects of changeability between euthymia and affect states (Anxiety/Depression, AD; Depression/Elation, DE; and Anger, Ang). The aim of our study was to investigate the psychometric characteristics of an Italian version of the ALS-18 in a sample of adults recruited from the general population. The sample was composed of 494 adults (343 women and 151 men) aged 18 and higher (mean age = 31.73 years, SD = 12.6). All participants were administered a checklist assessing socio-demographic variables, the ALS-18 and measures of depression and difficulties in emotion regulation. Confirmatory factor analyses indicated adequate fit of the three-factor model (RMSEA = 0.061, 95% CI = 0.054/0.069; CFI = 0.99; SRMR = 0.055), and the presence of a higher-order general factor. Internal consistency was satisfactory for all the lower-order dimensions and the general factor (ordinal α > 0.70). The ALS-18 was significantly associated with concurrent measures of depression and difficulties in emotion regulation. These findings indicate that the ALS-18 is a valid and reliable instrument for measuring affect lability, although discriminant validity of subdimensions scores could be problematic

Personality disorders and suicide: Risk factors and prevention

Personality disorders are a major risk factor for suicidal behavior. In psychological autopsy studies, individuals with personality disorders (especially borderline personality disorder) are common among suicides. We performed careful Pubmed, and PsycInfo searches from 1980 to 2010. Search terms were "suicide", "personality disorders", "suicide prevention" (and related terms). We identified studies dealing with suicide and reviewed research on the following areas of interest: risk factors for suicide in personality disorders and intervention tactics to prevent suicide. \ua9 2012 by Nova Science Publishers, Inc. All rights reserved