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      Norfloxacin-Loaded Electrospun Scaffolds: Montmorillonite Nanocomposite vs. Free Drug

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          Abstract

          Infections in nonhealing wounds remain one of the major challenges. Recently, nanomedicine approach seems a valid option to overcome the antibiotic resistance mechanisms. The aim of this study was the development of three types of polysaccharide-based scaffolds (chitosan-based (CH), chitosan/chondroitin sulfate-based (CH/CS), chitosan/hyaluronic acid-based (CH/HA)), as dermal substitutes, to be loaded with norfloxacin, intended for the treatment of infected wounds. The scaffolds have been loaded with norfloxacin as a free drug (N scaffolds) or in montmorillonite nanocomposite (H—hybrid-scaffolds). Chitosan/glycosaminoglycan (chondroitin sulfate or hyaluronic acid) scaffolds were prepared by means of electrospinning with a simple, one-step process. The scaffolds were characterized by 500 nm diameter fibers with homogeneous structures when norfloxacin was loaded as a free drug. On the contrary, the presence of nanocomposite caused a certain degree of surface roughness, with fibers having 1000 nm diameters. The presence of norfloxacin–montmorillonite nanocomposite (1%) caused higher deformability (90–120%) and lower elasticity (5–10 mN/cm 2), decreasing the mechanical resistance of the systems. All the scaffolds were proven to be degraded via lysozyme (this should ensure scaffold resorption) and this sustained the drug release (from 50% to 100% in 3 days, depending on system composition), especially when the drug was loaded in the scaffolds as a nanocomposite. Moreover, the scaffolds were able to decrease the bioburden at least 100-fold, proving that drug loading in the scaffolds did not impair the antimicrobial activity of norfloxacin. Chondroitin sulfate and montmorillonite in the scaffolds are proven to possess a synergic performance, enhancing the fibroblast proliferation without impairing norfloxacin’s antimicrobial properties. The scaffold based on chondroitin sulfate, containing 1% norfloxacin in the nanocomposite, demonstrated adequate stiffness to sustain fibroblast proliferation and the capability to sustain antimicrobial properties to prevent/treat nonhealing wound infection during the healing process.

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          Most cited references39

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          The Wound Healing Process: An Overview of the Cellular and Molecular Mechanisms

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            Nanoparticle–Biofilm Interactions: The Role of the EPS Matrix

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              Chronic wound infection: facts and controversies.

              Chronic wound infections are responsible for considerable morbidity and significantly contribute to the escalation in the cost of health care. Wound infection may initially be manifest as bacterial colonization, and it is only when colonization is combined with other factors, such as decreased vascular supply, intrinsic virulence of specific bacteria (eg, Staphylococcus aureus), and host immune factors, that true infection occurs. The microbiology of chronic wounds is complex, and it is difficult to discern which bacteria are culpable. Deep cultures or quantitative biopsies of wound tissue may be necessary. In some instances, such as in the presence of certain mycobacteria, isolation of specific organisms confirms causation. In many instances, it is appropriate to treat these wounds empirically with a combination of topical antiseptics and systemic antibiotics, especially in the presence of invasive infections. Published by Elsevier Inc.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                04 April 2020
                April 2020
                : 12
                : 4
                : 325
                Affiliations
                [1 ]Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy; angela.faccendini@ 123456gmail.com (A.F.); marco.ruggeri02@ 123456universitadipavia.it (M.R.); dalila.miele@ 123456gmail.com (D.M.); silvia.rossi@ 123456unipv.it (S.R.); cbonferoni@ 123456unipv.it (M.C.B.); pietro.grisoli@ 123456unipv.it (P.G.); barbara.vigani@ 123456unipv.it (B.V.); franca.ferrari@ 123456unipv.it (F.F.)
                [2 ]Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Campus of Cartuja, 18071 Granada, Spain; carola@ 123456ugr.es (C.A.); cviseras@ 123456ugr.es (C.V.)
                Author notes
                [* ]Correspondence: giuseppina.sandri@ 123456unipv.it ; Tel.: +0039-0382-987728
                Author information
                https://orcid.org/0000-0001-9511-3857
                https://orcid.org/0000-0002-1194-9372
                https://orcid.org/0000-0001-6766-9321
                Article
                pharmaceutics-12-00325
                10.3390/pharmaceutics12040325
                7238150
                32260441
                ad95a7a2-d14d-4f48-b377-c58a54a23351
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 February 2020
                : 27 March 2020
                Categories
                Article

                electrospinning,chitosan,glycosaminoglycans,scaffolds,fibroblasts proliferation,antimicrobial properties

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