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Prussian Blue (PB) is an inexpensive, biocompatible, photothermally active material. In this paper, self-assembled monolayers of PB nanoparticles were grafted on a glass surface, protected with a thin layer of silica and decorated with spherical silver nanoparticles. This combination of a photothermally active nanomaterial, PB, and an intrinsically antibacterial one, silver, leads to a versatile coating that can be used for medical devices and implants. The intrinsic antibacterial action of nanosilver, always active over time, can be enhanced on demand by switching on the photothermal effect of PB using near infrared (NIR) radiation, which has a good penetration depth through tissues and low side effects. Glass surfaces functionalized by this layer-by-layer approach have been characterized for their morphology and composition, and their intrinsic and photothermal antibacterial effect was studied against Gram+ and Gram- planktonic bacteria.

Supplementary Materials: The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/ijms24043172/s1., Acknowledgments: The authors acknowledge ESRF (Grenoble, Fr) for beamtime allocation and financial support for X-ray experiments (doi:10.15151/ESRF-ES-585935736) and ID02 staff for their precious technical assistance. The authors also acknowledge Centro Grandi Strumenti of the University of Pavia, Teresa Recca and Massimo Boiocchi for the NMR and TEM analysis, Centro Interdipartimentale di Studi e Ricerche per la Conservazione del Patrimonio Culturale (CISRiC)—Arvedi Laboratory of the University of Pavia and Alessandro Girella for the SEM analysis, and Alfatest S.r.l. and Dario Bozzo for the SEM analysis of the bacteria., Tendon disorders are common medical conditions that could lead to significant disability, pain, healthcare costs, and a loss of productivity. Traditional approaches require long periods of treatment, and they largely fail due to the tissues weakening and the postoperative alterations of the normal joint mechanics. To overcome these limitations, innovative strategies for the treatment of these injuries need to be explored. The aim of the present work was the design of nano-fibrous scaffolds based on poly(butyl cyanoacrylate) (PBCA), a well-known biodegradable and biocompatible synthetic polymer, doped with copper oxide nanoparticles and caseinphosphopeptides (CPP), able to mimic the hierarchical structure of the tendon and to improve the tissue healing potential. These were developed as implants to be sutured to reconstruct the tendons and the ligaments during surgery. PBCA was synthetized, and then electrospun to produce aligned nanofibers. The obtained scaffolds were characterized for their structure and physico-chemical and mechanical properties, highlighting that CuO and CPP loading, and the aligned conformation determined an increase in the scaffold mechanical performance. Furthermore, the scaffolds loaded with CuO showed antioxidant and antiinflammatory properties. Moreover, human tenocytes adhesion and proliferation to the scaffolds were assessed in vitro. Finally, the antibacterial activity of the scaffolds was evaluated using Escherichia coli and Staphylococcus aureus as representative of Gram-negative and Gram-positive bacteria, respectively, demonstrating that the CuO-doped scaffolds possessed a significant antimicrobial effect against E. coli. In conclusion, scaffolds based on PBCA and doped with CuO and CPP deserve particular attention as enhancers of the tendon tissue regeneration and able to avoid bacterial adhesion. Further investigation on the scaffold efficacy in vivo will assess their capability for enhancing the tendon ECM restoration in view of accelerating their translation to the clinic.

Bacteria infections and related biofilms growth on surfaces of medical devices are a serious threat to human health. Controlled hyperthermia caused by photothermal effects can be used to kill bacteria and counteract biofilms formation. Embedding of plasmonic nano-objects like gold nanostars (GNS), able to give an intense photothermal effect when irradiated in the NIR, can be a smart way to functionalize a transparent and biocompatible material like polydimethylsiloxane (PDMS). This process enables bacteria destruction on surfaces of PDMS-made medical surfaces, an action which, in principle, can also be exploited in subcutaneous devices. We prepared stable and reproducible thin PDMS films containing controllable quantities of GNS, enabling a temperature increase that can reach more than 40 degrees. The hyperthermia exerted by this hybrid material generates an effective thermal microbicidal effect, killing bacteria with a near infrared (NIR) laser source with irradiance values that are safe for skin.

Background: Chronic cutaneous wounds represent a major issue in medical care and are often prone to infections. Purpose: The aim of this study was the design of a clay mineral-drug nanocomposite based on montmorillonite and norfloxacin (NF, antimicrobial drug) as a powder for cutaneous application, to enhance wound healing in infected skin lesions. Methods: The nanocomposite has been prepared by means of an intercalation solution procedure. Adsorption isotherm, solid-state characterization of the nanocomposite, drug loading capacity and its release have been performed. Moreover, cytocompatibility, in vitro fibroblast proliferation and antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus were assessed. Results: The clay drug adsorption isotherm demonstrates that the mechanism of NF intercalation into montmorillonite galleries is the adsorption as one single process, due to the charge–charge interaction between protonated NF and negatively charged montmorillonite edges in the interlayer space. Nanocomposite is biocompatible and it is characterized by antimicrobial activity greater than the free drug: this is due to its nanostructure and controlled drug release properties. Conclusion: Considering the results obtained, NF–montmorillonite nanocomposite seems a promising tool to treat infected skin lesions or skin wounds prone to infection, as chronic ulcers (diabetic foot, venous leg ulcers) and burns.

The aim of this work was the development of microstructured lipid carriers (MLC) based on chitosan (CH) and containing N-acetylcysteine (NAC), a mucolytic and antioxidant agent, to inhibit the formation of Pseudomonas aeruginosa biofilm. MLC were prepared using the high shear homogenization technique. The MLC were characterized for morphology, particle size, Z potential, encapsulation efficiency and drug release. The antioxidant properties of NAC-loaded microstructured carriers were evaluated through an in vitro spectrophotometer assay. Finally, the activity of NAC-CH-MLC on biofilm production by Pseudomonas aeruginosa was also evaluated. Results obtained from this study highlighted that the use of chitosan into the inner aqueous phase permitted to obtain microstructured particles with a narrow size range and with good encapsulation efficiency. NAC-loaded MLC showed higher antioxidant activity than the free molecule, demonstrating how encapsulation increases the antioxidant effect of the molecule. Furthermore, the reduction of biofilm growth resulted extremely high with MLC being 64.74% &plusmn, 6.2 and 83.74% &plusmn, 9.95, respectively, at 0.5 mg/mL and 2 mg/mL. In conclusion, this work represents a favorable technological strategy against diseases in which bacterial biofilm is relevant, such as cystic fibrosis.

The aim of this work was the development of microstructured lipid carriers (MLC) based on chitosan (CH) and containing N-acetylcysteine (NAC), a mucolytic and antioxidant agent, to inhibit the formation of Pseudomonas aeruginosa biofilm. MLC were prepared using the high shear homogenization technique. The MLC were characterized for morphology, particle size, Z potential, encapsulation efficiency and drug release. The antioxidant properties of NAC-loaded microstructured carriers were evaluated through an in vitro spectrophotometer assay. Finally, the activity of NAC-CH-MLC on biofilm production by Pseudomonas aeruginosa was also evaluated. Results obtained from this study highlighted that the use of chitosan into the inner aqueous phase permitted to obtain microstructured particles with a narrow size range and with good encapsulation efficiency. NAC-loaded MLC showed higher antioxidant activity than the free molecule, demonstrating how encapsulation increases the antioxidant effect of the molecule. Furthermore, the reduction of biofilm growth resulted extremely high with MLC being 64.74% ± 6.2% and 83.74% ± 9.95%, respectively, at 0.5 mg/mL and 2 mg/mL. In conclusion, this work represents a favorable technological strategy against diseases in which bacterial biofilm is relevant, such as cystic fibrosis.

Monolayers of the Cu2+ complex of a diamino–diamido ligand can be grafted on plain glass obtaining the pH-controlled release of the Cu2+ cation for antibacterial surfaces whose microbicidal effect is lowered by the neutral charge of the complex.

Peripheral artery occlusive disease is an emerging cardiovascular disease characterized by the blockage of blood vessels in the limbs and is associated with dysfunction, gangrene, amputation, and a high mortality risk. Possible treatments involve by-pass surgery using autologous vessel grafts, because of the lack of suitable synthetic small-diameter vascular prosthesis. One to five percent of patients experience vascular graft infection, with a high risk of haemorrhage, spreading of the infection, amputation and even death. In this work, an infection-proof vascular graft prototype was designed and manufactured by electrospinning 12.5% w/v poly-L-lactic-co-glycolic acid solution in 75% v/v dichloromethane, 23.8% v/v dimethylformamide and 1.2% v/v water, loaded with 0.2% w/wPLGA. Polymer and tobramycin concentrations were selected after viscosity and surface tension and after HPLC-UV encapsulation efficiency (EE%) evaluation, respectively. The final drug-loaded prototype had an EE% of 95.58% ± 3.14%, with smooth fibres in the nanometer range and good porosity; graft wall thickness was 291 ± 20.82 μm and its internal diameter was 2.61 ± 0.05 mm. The graft’s antimicrobic activity evaluation through time-kill assays demonstrated a significant and strong antibacterial activity over 5 days against Staphylococcus aureus and Escherichia coli. An indirect cell viability assay on Normal Human Dermal Fibroblasts (NHDF) confirmed the cytocompatibility of the grafts.

Francesca Saporito,1 Giuseppina Sandri,1 Maria Cristina Bonferoni,1 Silvia Rossi,1 Cinzia Boselli,1 Antonia Icaro Cornaglia,2 Barbara Mannucci,3 Pietro Grisoli,1 Barbara Vigani,1 Franca Ferrari1 1Department of Drug Sciences, University of Pavia, Pavia, 2Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, 3Centro Grandi Strumenti, University of Pavia, Pavia, Italy Abstract: Chronic wounds and severe burns are diseases responsible for severe morbidity and even death. Wound repair is a crucial process and tissue regeneration enhancement and infection prevention are key factors to minimize pain, discomfort, and scar formation. The aim of this work was the development of lipid nanoparticles (solid lipid nanoparticles and nanostructured lipid carriers [NLC]), to be loaded with eucalyptus or rosemary essential oils and to be used, as medical devices, to enhance healing of skin wounds. Lipid nanoparticles were based on natural lipids: cocoa butter, as solid lipid, and olive oil or sesame oil, as liquid lipids. Lecithin was chosen as surfactant to stabilize nanoparticles and to prevent their aggregation. The systems were prepared by high shear homogenization followed by ultrasound application. Nanoparticles were characterized for physical–chemical properties, bioadhesion, cytocompatibility, in vitro proliferation enhancement, and wound healing properties toward normal human dermal fibroblasts. Antimicrobial activity of nanoparticles was evaluated against two reference microbial strains, one of Staphylococcus aureus, the other of Streptococcus pyogenes. Finally, the capability of nanoparticles to promote wound healing in vivo was evaluated on a rat burn model. NLC based on olive oil and loaded with eucalyptus oil showed appropriate physical–chemical properties, good bioadhesion, cytocompatibility, in vitro proliferation enhancement, and wound healing properties toward fibroblasts, associated to antimicrobial properties. Moreover, the in vivo results evidenced the capability of these NLC to enhance the healing process. Olive oil, which is characterized by a high content of oleic acid, proved to exert a synergic effect with eucalyptus oil with respect to antimicrobial activity and wound repair promotion. Keywords: lipid nanoparticles, eucalyptus essential oil, antimicrobial properties, wound healing

The aim of the present work was the development of polymer films loaded with a carvacrol (CVR)/clay hybrid (HYBD) for the delivery of CRV in infected skin ulcer treatment. Different clays were considered: montmorrilonite, halloysite and palygorskite (PHC). CRV incorporation in PHC reduced its volatility. HYBD showed 20% w/w CRV loading capacity and was able to preserve CRV antioxidant properties. HYBD was characterized by improved antimicrobial properties against S. aureus and E. coli and cytocompatibility towards human fibroblasts with respect to pure CRV. Films were prepared by casting an aqueous dispersion containing poly(vinylalcohol) (PVA), poly(vinylpyrrolidone) (PVP), chitosan glutamate (CS), sericin and HYBD. Optimization of film composition was supported by a Design of Experiments (DoE) approach. In a screening phase, a full factorial design (FFD) was used and the following factors were investigated at two levels: PVA (12-14%w/w), PVP (2-4%w/w) and CS (0.134-0.5%w/w) concentrations. For the optimization phase, FFD was expanded to a "central composite design". The response variables considered were: elongation, tensile strength and buffer absorption of films, durability of the gels formed after film hydration. Upon hydration, the optimized film formed a viscoelastic gel able to protect the lesion area and to modulate CRV release.

We developed an easy and reproducible synthetic method to graft a monolayer of copper sulfide nanoparticles (CuS NP) on glass and exploited their particular antibacterial features. Samples were fully characterized showing a good stability, a neat photo-thermal effect when irradiated in the Near InfraRed (NIR) region (in the so called &ldquo, biological window&rdquo, ), and the ability to release controlled quantities of copper in water. The desired antibacterial activity is thus based on two different mechanisms: (i) slow and sustained copper release from CuS NP-glass samples, (ii) local temperature increase caused by a photo-thermal effect under NIR laser irradiation of CuS NP&ndash, glass samples. This behavior allows promising in vivo applications to be foreseen, ensuring a &ldquo, static&rdquo, antibacterial protection tailored to fight bacterial adhesion in the critical timescale of possible infection and biofilm formation. This can be reinforced, when needed, by a photo-thermal action switchable on demand by an NIR light.

Chronic wounds account for 3% of total healthcare expenditure of developed countries; thus, innovative therapies, including Mesenchymal Stem Cells (MSCs) end their exosomes are increasingly considered, even if the activity depends on the whole secretome, made of both soluble proteins and extracellular vesicles. In this work, we prove for the first time the in vivo activity of the whole secretome formulated in a sponge-like alginate wound dressing to obtain the controlled release of bioactive substances. The product has been prepared in a public GMP-compliant facility by a scalable process; based on the murine model, treated wounds healed faster than controls without complications or infections. The treatment induced a higher acute inflammatory process in a short time and sustained the proliferative phase by accelerating fibroblast migration, granulation tissue formation, neovascularization and collagen deposition. The efficacy was substantially supported by the agreement between histological and proteomic findings. In addition to functional modules related to proteolysis, complement and coagulation cascades, protein folding and ECM remodeling, in treated skin, emerged the role of specific wound healing related proteins, including Tenascin (Tnc), Decorin (Dcn) and Epidermal growth factor receptor (EGFR). Of note, Decorin and Tenascin were also components of secretome, and network analysis suggests a potential role in regulating EGFR. Although further experiments will be necessary to characterize better the molecular keys induced by treatment, overall, our results confirm the whole secretome efficacy as novel "cell-free therapy". Also, sponge-like topical dressing containing the whole secretome, GMP- compliant and "ready-off-the-shelf", may represent a relevant point to facilitate its translation into the clinic.

Hibiscus sabdariffa L. is a tropical plant belonging to the Malvaceae family. In Kurdistan, the Autonomous Region of Iraq, water infusion of H. sabdariffa calyces is recommended for the treatment of hypotension and the common cold. Three distillation techniques: hydrodistillation (HD), steam distillation (SD), and solvent-free microwave-assisted extraction (SFME) have been compared to obtain the essential oils from calyces. The composition of the extracts was investigated by GC-FID and GC-MS. A total of 62 compounds have been identified, from which 55 components were found in HD distillates (95.75%), 37 components in SFME (96.06%), and 29 in SD (99.63%). Chemometric tools were applied to optimise and evidence the relation between distillation techniques and composition of the obtained essential oils as an investigation for the essential oils commercialisation approach of Hibiscus sabdariffa L. that have been done from a long time using conventional hydrodistillation in the local Herbal and Tea markets in Kurdistan.

Local administration of vaginal probiotics, especially lactobacilli, has been recently proposed as an effective prevention strategy against candidosis recurrences, which affect 40&ndash, 50% of women. In this context, the aim of the present work was the development of a mucoadhesive in situ gelling formulation for the vaginal administration of Lactobacillus gasseri. Mixtures of poloxamer 407 (P407) and methylcellulose (MC), two thermosensitive polymers, were prepared and subjected to rheological analyses for the assessment of their sol/gel transition temperature. The association of P407 (15% w/w) with MC (1.5% w/w) produced an increase in gelation extent at 37 &deg, C even after dilution in simulated vaginal fluid (SVF). The presence of 0.5% w/w pectin (PEC) produced a reduction of vehicle pH and viscosity at 25 &deg, C that is the vehicle resistance to flow during administration. The presence of a low concentration of xyloglucan (XYL) (0.25% w/w) increases the mucoadhesive properties and the capability to gelify at 37 &deg, C of the formulation after dilution with SVF. A three-component (P407/MC/PEC, 3cM) and a four-component (P407/MC/PEC/XYL, 4cM) mixture were selected as promising candidates for the delivery of L. gasseri to the vaginal cavity. They were able to preserve L. gasseri viability and were cytocompatible towards the HeLa cell line.

Anti-infective surfaces are a modern strategy to address the issue of infection related to the clinical use of materials for implants and medical devices. Nanocoatings, with their high surface/mass ratio, lend themselves to being mono-layered on the material surfaces to release antibacterial molecules and prevent bacterial adhesion. Here, a &ldquo, layer-by-layer&rdquo, (LbL) approach to achieve a self-assembled monolayer (SAM) with high microbicidal effect on hydroxylated surfaces is presented, exploiting the reaction between a monolayer of thiolic functions on glass/quartz surfaces and a newly synthesized derivative of the well-known antibacterial compound silver sulfadiazine. Using several different techniques, it is demonstrated that a nano-monolayer of silver sulfadiazine is formed on the surfaces. The surface-functionalized materials showed efficient bactericidal effect against both Gram-positive and Gram-negative bacteria. Interestingly, bactericidal self-assembled nano-monolayers of silver sulfadiazine could be achieved on a large variety of materials by simply pre-depositing glass-like SiO2 films on their surfaces.

The adhesion and proliferation of bacteria on abiotic surfaces pose challenges in both health care and industrial applications. Gold nanostars (GNSs) monolayers grafted on glass have demonstrated to exert antibacterial action due to their photo-thermal features. Here, these GNS layers were further functionalized using thiols monolayers, in order to impart different wettability to the surfaces and thus adding a feature that could help to fight bacterial proliferation. Thiol that has different functional groups was used and the thiol-protected surfaces were characterized by means of UV-vis spectroscopy, contact angles, SEM and surface enhanced Raman spectroscopy (SERS). We verified that (i) coating with the proper thiol allows us to impart high hydrophilicity or hydrophobicity to the surfaces (with contact angle values ranging from 10 to 120&deg, ), (ii) GNS monolayers are strongly stabilized by functionalization with thiols, with shelf stability increasing from a few weeks to more than three months and (iii) photo-thermal features and subsequent antibacterial effects caused by hyperthermia are not changed by thiols layers, allowing us to kill at least 99.99% of representative bacterial strains.

Cutaneous wounds represent a major issue in medical care, with approximately 300 million chronic and 100 million traumatic wound patients worldwide, and microbial infections slow the healing process. The aim of this work was to develop electrospun scaffolds loaded with silver nanoparticles (AgNPs) to enhance cutaneous healing, preventing wound infections. AgNPs were directly added to polymeric blends based on chitosan (CH) and pullulan (PUL) with hyaluronic acid (HA) or chondroitin sulfate (CS) to be electrospun obtaining nanofibrous scaffolds. Moreover, a scaffold based on CH and PUL and loaded with AgNPs was prepared as a comparison. The scaffolds were characterized by chemico&ndash, physical properties, enzymatic degradation, biocompatibility, and antimicrobial properties. All the scaffolds were based on nanofibers (diameters about 500 nm) and the presence of AgNPs was evidenced by TEM and did not modify their morphology. The scaffold degradation was proven by means of lysozyme. Moreover, the AgNPs loaded scaffolds were characterized by a good propensity to promote fibroblast proliferation, avoiding the toxic effect of silver. Furthermore, scaffolds preserved AgNP antimicrobial properties, although silver was entrapped into nanofibers. Chitosan/chondroitin sulfate scaffold loaded with AgNPs demonstrated promotion of fibroblast proliferation and to possess antimicrobial properties, thus representing an interesting tool for the treatment of chronic wounds.

Natural polymers represent a promising family of materials for the fabrication of skin wound dressings that can improve the healing process and the protection against pathogens. In this work, we present the preparation of natural polymeric films combining two plant-based polymers: zein, an alcohol-soluble protein from corn, and pectin, a hydrophilic polysaccharide of the plant cell wall. The effect of two different forms of pectin – low methoxy and amidated low methoxy – on the resulting biocomposite was investigated. Glycerol was added to improve the mechanical performances. The degradation assay in various buffers and thermogravimetric analysis highlighted the tendency of the composite films to degrade faster in water than the pure zein films, due to the pectin ability to be released from the protein matrix in an aqueous environment. Drug release was performed, confirming the results obtained with previous analyses. Antimicrobial assays indicated the ability of the developed biocomposite patches to inhibit the growth of three pathogens (Escherichia coli, Staphylococcus aureus, Candida albicans). The biocompatibility was confirmed in vitro with primary human dermal fibroblasts via MTS assay and cell morphology inspection. The results indicate the great potential of the presented plant-based biomaterials as drug delivery systems for the treatment of skin wounds.

This work aims at designing a drug delivery system for rifampicin (RIF) to be used for the therapy of infections from mycobacterium tuberculosis or other lung-colonizing bacteria. We are proposing, in particular, the delivery of RIF by micelles based on inulin functionalized with vitamin E (INVITE). We previously demonstrated that INVITE micelles are formed from the self-assembling sustained by the interaction, within the hydrophobic core, of aromatic groups belonging to vitamin E. It points on the effectiveness of these biocompatible systems in incorporating aromatic-group-bearing hydrophobic drug such as RIF. The succinilated derivative of INVITE, namely INVITESA, was further studied. Other than a full physicochemical characterization, the obtained micelles containing RIF were tested for their antibacterial activity against Gram- or Gram+bacteria including mycobacterium smegmatis. Furthermore, uptake studies on human alveolar macrophages and MTT studies were performed.

We developed a reproducible synthetic method to grow anisotropic silver nanoplates on glass, giving them the desired plasmonic features and tuning their size and LSPR absorption with growth time. Samples were fully characterized showing good stability, a strong photo-thermal effect and the ability to release controlled quantities of silver in water. These samples showed a strong antibacterial activity, which is based on two different mechanisms: silver ion release and hyperthermia caused by the photo-thermal effect under near-infrared laser irradiation. This behaviour allows us to foresee promising in vivo applications, ensuring a long-term antibacterial protection which can be reinforced, when needed, by a fast photo-thermal action which can be switched on by a NIR laser treatment.

Phyllanthus muellerianus (Kuntze) Excell (family Euphorbiaceae) stem bark methanol extract inhibited the growth of Clostridium sporogenes and Streptococcus pyogenes, responsible for gas gangrene and suppurative and non suppurative diseases, respectively. After the HPLC fingerprint acquisition a bioguided fractionation of the defatted methanol extract allowed the isolation of six fractions whose activity was evaluated against the two pathogen bacteria. A further purification of the most active fraction afforded a pure compound responsible for the very interesting inhibitory activity against C. sporogenes and S. pyogenes (MIC 0.91 μM, MIC 3.64 μM). (1)H NMR and MS analytical techniques allowed the identification of the bioactive as Nitidine; this quaternary ammonium alkaloid was observed in the genus Phyllanthus for the first time. A study on Nitidine counter ion, performed using energy dispersive spectroscopy (EDS) coupled with scanning electron microscopy (SEM) was also carried out.

Photo-responsive antibacterial surfaces combining both on-demand photo-switchable activity and sustained biocidal release were prepared using sequential chemical grafting of nano-objects with different geometries and functions. The multi-layered coating developed incorporates a monolayer of near-infrared active silica-coated gold nanostars (GNS) decorated by silver nanoparticles (AgNP). This modular approach also enables us to unravel static and photo-activated contributions to the overall antibacterial performance of the surfaces, demonstrating a remarkable synergy between these two mechanisms. Complementary microbiological and imaging evaluations on both planktonic and surface-attached bacteria provided new insights on these distinct but cooperative effects.

In the treatment of chronic wounds, topical application of anti-infective drugs such as silver sulfadiazine (AgSD) is of primary importance to avoid infections and accelerate wound repair. AgSD is used in burns and chronic wounds for its wide antibacterial spectrum, but presents limitations due to poor solubility and cytotoxicity. In the present work polymeric micelles obtained by self-assembling of chitosan ionically modified by interaction with oleic acid were developed as carriers for AgSD to overcome the drawbacks of the drug. The AgSD loaded micelles were intended to be associated in wound healing with platelet lysate (PL), a hemoderivative rich in growth factors. Unloaded micelles demonstrated good compatibility with both fibroblasts and PL. The relevance of chitosan concentration and of the ratio between chitosan and oleic acid to the drug loading and the particle size of nanoparticles was studied. A marked increase (up to 100 times with respect to saturated solution) of AgSD concentration in micelle dispersion was obtained. Moreover, the encapsulation reduced the cytotoxic effect of the drug towards fibroblasts and the drug incompatibility with PDGF-AB (platelet derived growth factor), chosen as representative of platelet growth factors.

Hydrodistillation of Xylopia hypolampra Mildbr. stem bark afforded 39 mg (dry weight basis) of a pale yellow fragrant essential oil; gas chromatography-flame ionization detector and gas chromatogra...

Silver compounds and especially silver sulfadiazine (AgSD) are reported as effective antimicrobial agents against almost all known bacteria, fungi and some viruses. However, AgSD has been shown to be cytotoxic toward fibroblasts and keratinocytes in vitro and consequently to retard wound healing in vivo. The aim of the present work was to evaluate the in vitro biocompatibility (cytotoxicity and proliferation), antimicrobial efficacy and cell motility gap closure (assay of wound closure) of MT/CS nanocomposites loaded with silver sulfadiazine (AgSD). It is envisioned to be administered as a powder or a dressing for cutaneous application in the treatment of skin ulcers. The loading of AgSD in MT/CS nanocomposites aimed at preventing the delay in wound healing, by decreasing the cytotoxicity of AgSD and maintaining its antimicrobial properties. Nanocomposites were prepared by using different amounts of MT (100-2000 mg) and 40 ml of a 1% (w/w) chitosan glutamate aqueous solution. The relative amounts of AgSD and chitosan in the systems were assessed by suitable analytic methods. The nanocomposite prepared using 100mg of MT was characterized for in vitro biocompatibility and proliferation and for wound healing using normal human dermal fibroblasts (NHDF). Antimicrobial properties were evaluated against four reference bacterial strains: Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Pseudomonas aeruginosa. AgSD loaded in the 100 MT/CS nanocomposite showed good in vitro biocompatibility and gap closure properties (fibroblasts) and maintained AgSD antimicrobial properties, especially against P. aeruginosa, that often complicates skin lesions.

The management of difficult to heal wounds can considerably reduce the time required for tissue repairing and promote the healing process, minimizing the risk of infection. Silver compounds, especially silver sulfadiazine (AgSD), are often used to prevent or to treat wound colonization, also in presence of antibiotic-resistant bacteria. However, AgSD has been shown to be cytotoxic in vitro toward fibroblasts and keratinocytes and consequently to retard wound healing in vivo. Recently, platelet lysate (PL) has been proposed in clinical practice for the healing of persistent lesions. The aim of the present work was the development of wound dressings based on AgSD loaded in solid lipid nanoparticles (SLNs), to be used in association with PL for the treatment for skin lesions. SLN were based on chondroitin sulfate and sodium hyaluronate, bioactive polymers characterized by well-known tissue repairing properties. The encapsulation of AgSD in SLN aimed at preventing the cytotoxic effect of the drug on normal human dermal fibroblasts (NHDFs) and at enabling the association of the drug with PL. SLN were loaded in wound dressings based on hydroxypropylmethyl cellulose (HPMC) or chitosan glutamate (CS glu). These polymers were chosen to obtain a sponge matrix with suitable elasticity and softness and, moreover, with good bioadhesive behavior on skin lesions. Dressings based on chitosan glutamate showed antimicrobial activity with and without PL. Even though further in vivo evaluation could be envisaged, chitosan based dressings demonstrated to be a suitable prototype for the treatment for skin lesions.

Aqueous, methanolic and ethyl acetate extracts of Piptadeniastrum africanum (Hook f.) Brenan stem bark were tested against fungi and representatives of Gram-positive and Gram-negative bacteria. Aqueous and methanolic extracts showed a maximum activity against the fungus Pyricularia grisea, a weak activity against the bacteria Staphylococcus aureus and Streptococcus mutans, while no activity was observed against Gram-negative bacteria. Ethyl acetate extract resulted inactive against all the tested microorganisms. Phytochemical investigations of the most active methanolic extract highlighted the presence of tannins and saponins. After purification by means of Sephadex LH-20 and RP-18 the tannin fraction resulted more active against bacteria, while the saponin fraction showed a pronounced activity against Pyricularia grisea. Five different strains of Pyricularia grisea were used and results show that the saponin fraction is promisingly active on the whole population (MIC and MFC: 0.03–0.06 mg mL−1). The saponin fraction fungicidal activity was similar to that of Flutriafol (0.01–0.04 mg mL−1), a commercially available fungicide, indicating that P. africanum stem bark extract can be a good candidate for the control of Pyricularia grisea, the most diffused rice blast disease fungus of rice.

A photo-responsive antibacterial surface was prepared grafting non-toxic Prussian blue nanoparticles on a functionalized glass surface. Colloidal Prussian blue was synthesized as nanoparticles with cubic shape and grafted on a polyamine-functionalized SiO2 surface, obtaining a good coverage and a homogeneous distribution of the nanocubes. Irradiation of these samples in the so-called ‘bio-transparent window’ of the near-infrared allows to exert a triggered antibacterial effect.

In the present work, we describe a simple procedure to produce biomimetically coated silver nanoparticles (Ag NPs), based on the postfunctionalization and purification of colloidal silver stabilized by citrate. Two biological capping agents have been used (cysteine Cys and glutathione GSH). The composition of the capped colloids has been ascertained by different techniques and antibacterial tests on GSH-capped Ag NPs have been conducted under physiological conditions, obtaining values of Minimum Inhibitory Concentration (MIC) of 180 and 15 μg/mL for Staphylococcus aureus and Escherichia coli, respectively. The antibacterial activity of these GSH capped NPs can be ascribed to the direct action of metallic silver NPs, rather than to the bulk release of Ag(+).

Functional and bioactive properties of a selection of chitosan and hyaluronic acid grades were compared to enable a rational choice of the best candidate for the future development of mucoadhesive systems intended for the treatment of buccal or vaginal mucositis. Chitosan or hyaluronic acid molecular weight, type of salt and the pH of the administration site were considered as critical variables for functional and bioactive polymer properties. Two grades of chitosan, salified with ascorbic acid or hydrochloric acid, and two grades of sodium hyaluronate were examined. Aqueous solutions (1 % w/w) of each polymer grade or salt were prepared and compared for viscosity, mucoadhesive (tensile stress measurements), antimicrobial, antioxidant and tissue repairing properties. The overall comparison of the results indicates that the high molecular weight of chitosan ascorbate is the more promising candidate for the development of mucoadhesive formulations, characterized by bioactive properties.

Badam Talkh kuhi is an endemic species of Iran commonly used by native people as anti-inflammatory and an- timicrobial remedy. The present study was aimed at investigating the folk claims of this plant, identified by us as Amygdalus lycioides Spach. Several extracts were prepared using various extraction procedures combined with solvents of different polarity. A decoction was firstly prepared according to the procedure of the folk medicine. Maceration (ME), Ul- trasound-Assisted Extraction (USAE) and Microwave-Assisted Solvent Extraction (MASE) were then experimented using pure methanol (MeOH) and n-hexane-acetone (n-Hex-Ac, 50% v/v). Concerning biological investigation, the antimicro- bial potential of all extracts was firstly evaluated by employing the growth inhibition test. Then, the free radical scaveng- ing effect of each extract was measured, given that reactive oxygen species (ROS) are involved in TNF� -induced signal- ing pathways associated with inflammation. Finally, the anti-TNFactivity of the most active extracts was evaluated us- ing in vitro and in vivo assays. Regarding the anti-inflammatory activity, decoction and MASE n-Hex/Ac extract inhibited the production of TNFwith IC50 in the range of 120-390 � g/ml and 6-20 � g/ml, respectively. Interestingly, after oral administration in mice, MASE n-Hex/Ac extract was effective in reducing TNFof about 60%. Moreover, treated animals did not show any signs of toxicity. Results herein reported clearly evidenced that Amygdalus lycioides Spach could be a valuable source of TNF� -blockers effective against chronic inflammatory diseases.