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      A Chitosan—Based Liposome Formulation Enhances the In Vitro Wound Healing Efficacy of Substance P Neuropeptide

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          Abstract

          Currently, there is considerable interest in developing innovative biodegradable nanoformulations for controlled administration of therapeutic proteins and peptides. Substance P (SP) is a neuropeptide of 11 amino acids that belongs to the tachykinins family and it plays an important role in wound healing. However, SP is easily degradable in vivo and has a very short half-life, so the use of chitosan-based nanocarriers could enhance its pharmaceutical properties. In light of the above, the aim of this work was to produce and characterize chitosan-coated liposomes loaded with SP (SP-CH-LP) as novel biomaterials with potential application in mucosal wound healing. The loaded system’s biophysical properties were characterized by dynamic light scattering with non-invasive back scattering (DLS-NIBS), mixed mode measurements and phase analysis light scattering (M3-PALS) and high performance liquid chromatography with ultraviolet/visible light detection (HPLC-UV/VIS). Then, the efficacy of the obtained nanoformulations was examined via proof-of-principle experiments using in vitro cell assays. These assays showed an increment on cell motility and proliferation after treatment with free and encapsulated neuropeptides. Additionally, the effect of SP on wound healing was enhanced by the entrapment on CH-LP. Overall, the amenability of chitosan-based nanomaterials to encapsulate peptides and proteins constitutes a promising approach towards potential novel therapies to treat difficult wounds.

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          Most cited references 53

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          Regulation of wound healing by growth factors and cytokines.

          Cutaneous wound healing is a complex process involving blood clotting, inflammation, new tissue formation, and finally tissue remodeling. It is well described at the histological level, but the genes that regulate skin repair have only partially been identified. Many experimental and clinical studies have demonstrated varied, but in most cases beneficial, effects of exogenous growth factors on the healing process. However, the roles played by endogenous growth factors have remained largely unclear. Initial approaches at addressing this question focused on the expression analysis of various growth factors, cytokines, and their receptors in different wound models, with first functional data being obtained by applying neutralizing antibodies to wounds. During the past few years, the availability of genetically modified mice has allowed elucidation of the function of various genes in the healing process, and these studies have shed light onto the role of growth factors, cytokines, and their downstream effectors in wound repair. This review summarizes the results of expression studies that have been performed in rodents, pigs, and humans to localize growth factors and their receptors in skin wounds. Most importantly, we also report on genetic studies addressing the functions of endogenous growth factors in the wound repair process.
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            Antimicrobial properties of chitosan and mode of action: a state of the art review.

            Owing to its high biodegradability, and nontoxicity and antimicrobial properties, chitosan is widely-used as an antimicrobial agent either alone or blended with other natural polymers. To broaden chitosan's antimicrobial applicability, comprehensive knowledge of its activity is necessary. The paper reviews the current trend of investigation on antimicrobial activities of chitosan and its mode of action. Chitosan-mediated inhibition is affected by several factors can be classified into four types as intrinsic, environmental, microorganism and physical state, according to their respective roles. In this review, different physical states are comparatively discussed. Mode of antimicrobial action is discussed in parts of the active compound (chitosan) and the target (microorganisms) collectively and independently in same complex. Finally, the general antimicrobial applications of chitosan and perspectives about future studies in this field are considered. Copyright © 2010 Elsevier B.V. All rights reserved.
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              Liposomes as nanomedical devices

              Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the “first-generation” liposomes, and liposome-based drugs on the market and in clinical trials.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                06 December 2017
                December 2017
                : 9
                : 4
                Affiliations
                [1 ]Institute of Plant Biology and Biotechnology (IBBP), Westfälische Wilhelms-Universität Münster, Schlossplatz 8, 48149 Münster, Germany; tamara.mengoni@ 123456gmail.com (T.M.); m_adri02@ 123456uni-muenster.de (M.A.); ssoar_01@ 123456uni-muenster.de (S.P.); mathiaskaiser@ 123456uni-muenster.de (M.K.)
                [2 ]ChiPrO GmbH, Anne-Conway-Strasse 1, 28359 Bremen, Germany; bcarballal@ 123456chipro.de or b_sant01@ 123456uni-muenster.de
                [3 ]School of Food Science & Nutrition, University of Leeds, Leeds LS2 9JT, UK
                Author notes
                [* ]Correspondence: F.M.Goycoolea@ 123456leeds.ac.uk ; Tel.: +44-(0)113-343-1412
                Article
                pharmaceutics-09-00056
                10.3390/pharmaceutics9040056
                5750662
                29211047
                © 2017 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/).

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