1,720,997 research outputs found

    Photothermal nanofibrillar membrane based on hyaluronic acid and graphene oxide to treat Staphylococcus aureus and Pseudomonas aeruginosa infected wounds

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    Here we reported the fabrication of an electrospun membrane based on a hyaluronic acid derivative (HA-EDA) to be used as a bandage for the potential treatment of chronic wounds. The membrane, loaded with graphene oxide (GO) and ciprofloxacin, showed photothermal properties and light-triggered drug release when irradiated with a near-infrared (NIR) laser beam. Free amino groups of HA-EDA derivative allowed autocrosslinking of the elec- trospun membrane; thus, a substantial enhancement in the hydrolytic resistance of the patch was obtained. In vitro antibacterial activity studies performed on Staphylococcus aureus and Pseudomonas aeruginosa revealed that such electrospun membranes, due to the synergistic effect of the antibiotic and NIR-mediated hyperthermia, reduced the viability of both pathogens. Specific in vitro experiment demonstrated also that is possible to disrupt, through laser irradiation, the biofilms formed onto the membrane

    A hyaluronic acid/cyclodextrin based injectable hydrogel for local doxorubicin delivery to solid tumors

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    Localized delivery of anticancer drugs is often the most useful therapeutic approach for the treatment of solid tumors. The use of injectable polymeric systems that maximize drug concentration in the proximal area of the tumor represents an extremely advantageous therapeutic strategy. Here, the development of an injectable in situ forming hydrogel was accomplished by exploiting the azo-type Michael reaction between an amine derivative of hyaluronic and vinylsulfone functionalized -cyclodextrins complexing doxorubicin. This injectable system can be easily prepared and administered with timelines compatible with normal operating room procedures, as demonstrated by rheological tests. In vitro experiments revealed that the peculiar physicochemical properties of the hydrogel guarantee a sustained release of the anticancer drug that blocks the growth of colorectal carcinoma micromasses cultured in 3D conditions. In vivo studies have confirmed that the medicated hydrogel can drastically reduce the tumor mass in the animal model without causing cytotoxic side effects in other areas of the body such as the heart. Overall, the proposed system has shown promising characteristics that make it an interesting useful device for localized chemotherapy of solid tumors

    Physicochemical and rheological characterization of different low molecular weight gellan gum products and derived ionotropic crosslinked hydrogels

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    A series of four different low molecular weight gellan gum products was obtained by alkaline hydrolysis with the aim to investigate the impact of the molecular weight on the rheological properties of the polysaccharide aqueous dispersions and on the physicochemical characteristics of derived ionotropic crosslinked hydrogels. In particular, thermo-rheological analysis was conducted on aqueous dispersions to study the influence of molecular weight on the thermogelation properties typical of the native polysaccharide while strain sweep experiments were conducted to establish if aqueous dispersion shows a viscoelastic behavior. The effect of different Ca2+ on the rheological properties of hydrogels were studied. Furthermore, ionotropic crosslinked hydrogels were analyzed in terms of morphology on the dried state and swelling behavior, while their viscoelastic properties were studied by means of rheological analysis conducted in frequency sweep regime after different time points of incubation in phosphate buffer at pH 7.4. Release experiments conducted using fluorescein isothiocyanate labelled dextran as a model diffusion agent and was performed to investigate the possibility of using the low molecular weight GG-derived hydrogels as an active molecule-releasing device. Finally, the cytocompatibility of hydrolysis products was investigated, as well as the capacity of hydrogels to encapsulate viable MC3T3-E1 preosteoblastic cells

    Development of stimulus-sensitive electrospun membranes based on novel biodegradable segmented polyurethane as triggered delivery system for doxorubicin

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    In this work, redox-sensitive polyurethane urea (PUU) based electrospun membranes have been exploited to chemically tether a pH-sensitive doxorubicin derivative achieved by linking a lipoyl hydrazide to the drug via a hydrazone linkage. First, the lipoyl-hydrazone-doxorubicin derivative labelled as LA-Hy-Doxo has been syn- thesized and characterized. Then, the molecule has been tethered, via a thiol-disulfide exchange reaction, to the redox-sensitive PUU (PolyCEGS) electrospun membrane. The redox-sensitive PolyCEGS PUU has been produced by using PCL-PEG-PCL polyol and glutathione-tetramethyl ester (GSSG-OMe)4 as a chain extender. The LA-Hy- Doxo tethered electrospun membrane has showed a dually controlled release triggered by acidic and reducing conditions, producing a significant cytotoxic effect in human breast cancer cell lines (MCF-7) which has validated the system for the post-surgical treatment of solid tumors to contrast recurrenc

    A self-sterilizing fluorescent Nanocomposite as versatile material with broad-spectrum Antibiofilm features

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    Hematogenous spread of infections from colonized central intravenous catheters or central lines is a long-recognized problem with infection rates of 2 and 6.8 per 1000 days, respectively. Besides, removal of severe microbial colonization of implanted biomaterials is still a challenge and usually requires invasive operations. Hence, on demand self-sterilizing materials are required to avoid explant of colonized biomaterials and improve patient compliance. Moreover, photoluminescence is needed to make trackable biomaterials, which can be easily monitored upon implanting them in the body. Here, we propose the incorporation of near infrared (NIR) sensitive red-emitting carbon nanodot (CDs) into a polymeric matrix to give rise to innovative biomaterials with self-tracking and photothermal antimicrobial abilities. We obtain a material which can be processed to obtain medical devices using different techniques, among which, for instance, electrospinning. Herein, a proof-of-concept preparation of electrospun scaffolds is reported as it is highly desired in biomedical applications. Beside to confer imaging properties to the scaffold, that would allow an easy control over the in vivo positioning of implanted biomaterials as well as its degradation state and grade of integration with the surrounding native tissues, thanks to the capability to convert NIR light into local heat CDs can be exploited to exert broad-spectrum antimicrobial effect toward several pathogens. The rise in temperature can be easily modulated by controlling the irradiation time to achieve both an in vitro self-sterilization of the device and eventually in vivo destabilization of the microbial colonization. This innovative biomaterial could successfully inhibits biofilm formation and might be used as a powerful tool to treat antibiotic-resistant nature of biofilm-related infections in implanted medical devices

    HYALURONIC ACID BASED-MICELLES FOR OFF-LABEL USE OF IMATINIB IN RETINOPATHIES TREATMENT

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    The aim of this work was to obtain polymeric micelles able to cross corneal barrier and to improve the permeation of imatinib free base. Micelles were prepared by using hyaluronic acid (HA) derivatives containing ethylenediamine (EDA), chains of hexadecyl (C16), polyethylene glycol (PEG) and/or L-carnitine (CRN). The resulting samples, named as HA-EDA-C16, HA-EDA-C16-PEG and HA-EDA-C16-CRN micelles, were designed to allow a non-invasive way of administration, i.e. topical ocular instillation. These nanocarriers showed an optimal particle size in aqueous media and mucoadhesive properties. Imatinib-loaded micelles were able to interact with corneal barrier and to promote imatinib transcorneal permeation and penetration. An interesting in vitro study was conducted to investigate imatinib inhibitory effect on a choroideal neovascularization process (1). Imatinib was able to inhibit endothelial cell sprouting and to reduce the formation of functional vessels. In addition, imatinib released from polymeric micelles was able to inhibit cell tube formation and to promote cell tube disruption. Obtained results suggested that prepared micelles could represent optimal candidates for off-label use of imatinib in the treatment of retinopathies

    Imatinib-Loaded Micelles of Hyaluronic Acid Derivatives for Potential Treatment of Neovascular Ocular Diseases

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    In this work, new micellar systems able to cross corneal barrier and to improve the permeation of imatinib free base were prepared and characterized. HA-EDA-C16, HA-EDA-C16−PEG, and HA-EDA-C16−CRN micelles were synthesized starting from hyaluronic acid (HA), ethylenediamine (EDA), hexadecyl chains (C16), polyethylene glycol (PEG), or L-carnitine (CRN). These nanocarriers showed optimal particle size and mucoadhesive properties. Imatinibloaded micelles were able to interact with corneal barrier and to promote imatinib transcorneal permeation and penetration. In addition, a study was conducted to understand the in vitro imatinib inhibitory effect on a choroidal neovascularization process. Imatinib released from polymeric micelles was able to inhibit endothelial cell sprouting and to promote cell tube disruption

    Production of a double layer scaffold for the “on demand” release of fibroblast-like limbal stem cells

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    The production and characterization of a double layer scaffold, to be used as a system for the “on demand” release of corneal limbal stem cells are here reported. The devices used in the clinics and proposed so far in the scientific literature, for the release of corneal stem cells in the treatment of limbal stem cell deficiency, cannot control the in vivo space-time release of cells since the biomaterial of which they are composed is devoid of stimuli responsiveness features. Our approach was to produce a scaffold composed of two different polymeric layers that give the device the appropriate mechanical properties to be placed on the ocular surface and the possibility of releasing the stem cells following a non-invasive and cell-friendly treatment. This device consists of an electrospun micro fibrillar scaffold of poly-L-lactic acid coated by a polymeric film based on an amphiphilic derivative of hyaluronic acid sensitive to the ionic strength of the external medium and to the presence of a complexing agent. The latter represents the “sacrificial” cell containing layer of the scaffold that can be dissolved “on demand” by the treatment with a solution of cyclodextrins. The rapid removal of the external polymeric film from the device is exploited to control the space-time release of the cells. In vitro and ex vivo experiments showed that fibroblast-like limbal stem cells cultured on the scaffold without the use of the feeder layer maintained their characteristics of stem cells and can be released “on demand” on the culture well coated with Matrigel or on the decellularized bovine cornea, respectively
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