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      Curcumin-In-Deformable Liposomes-In-Chitosan-Hydrogel as a Novel Wound Dressing

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          Abstract

          A liposomes-in-hydrogel system as an advanced wound dressing for dermal delivery of curcumin was proposed for improved chronic wound therapy. Curcumin, a multitargeting poorly soluble active substance with known beneficial properties for improved wound healing, was incorporated in deformable liposomes to overcome its poor solubility. Chitosan hydrogel served as a vehicle providing superior wound healing properties. The novel system should assure sustained skin delivery of curcumin, and increase its retention at the skin site, utilizing both curcumin and chitosan to improve the therapy outcome. To optimize the properties of the formulation and determine the effect of the liposomal charge on the hydrogel properties, curcumin-containing deformable liposomes (DLs) with neutral (NDLs), cationic (CDLs), and anionic (ADLs) surface properties were incorporated in chitosan hydrogel. The charged DLs affected the hydrogel’s hardness, cohesiveness, and adhesiveness. Importantly, the incorporation of DLs, regardless of their surface charge, in chitosan hydrogel did not decrease the system’s bioadhesion to human skin. Stability testing revealed that the incorporation of CDLs in hydrogel preserved hydrogel´s bioadhesiveness to a higher degree than both NDLs and ADLs. In addition, CDLs-in-hydrogel enabled the most sustained skin penetration of curcumin. The proposed formulation should be further evaluated in a chronic wound model.

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          Most cited references38

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          Nanotechnology-Driven Therapeutic Interventions in Wound Healing: Potential Uses and Applications

          The chronic nature and associated complications of nonhealing wounds have led to the emergence of nanotechnology-based therapies that aim at facilitating the healing process and ultimately repairing the injured tissue. A number of engineered nanotechnologies have been proposed demonstrating unique properties and multiple functions that address specific problems associated with wound repair mechanisms. In this outlook, we highlight the most recently developed nanotechnology-based therapeutic agents and assess the viability and efficacy of each treatment, with emphasis on chronic cutaneous wounds. Herein we explore the unmet needs and future directions of current technologies, while discussing promising strategies that can advance the wound-healing field.
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            Role of edge activators and surface charge in developing ultradeformable vesicles with enhanced skin delivery.

            Transfersomes are highly efficient edge activator (EA)-based ultraflexible vesicles capable of, non-invasively, trespassing skin by virtue of their high, self-optimizing deformability. This investigation presents different approaches for the optimization of Transfersomes for enhanced transepidermal delivery of Diclofenac sodium (DS). Different methods of preparation, drug and lipid concentrations and vesicle compositions were employed, resulting in ultraflexible vesicles with diverse membrane characteristics. Evaluation of Transfersomes was implemented in terms of their shapes, sizes, entrapment efficiencies (EE%), relative deformabilities and in vitro skin permeation. Transfersomes prepared with 95:5% (w/w) (PC:EA) ratio showed highest EE% (Span 85>Span 80>Na cholate>Na deoxycholate>Tween 80). Whereas, those prepared using 85:15% (w/w) ratio showed highest deformability (Tween 80 was superior to bile salts and spans). Transfersomes were proved significantly superior in terms of, the amount of drug deposited in the skin and the amount permeated, with an enhancement ratio of 2.45, when compared to a marketed product. The study proved that the type and concentration of EA, as well as, the method of preparation had great influences on the properties of Transfersomes. Hence, optimized Transfersomes can significantly increase transepidermal flux and prolong the release of DS, when applied non-occlusively. Copyright 2010 Elsevier B.V. All rights reserved.
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              Antimicrobial hydrogels: a new weapon in the arsenal against multidrug-resistant infections.

              The rapid emergence of antibiotic resistance in pathogenic microbes is becoming an imminent global public health problem. Treatment with conventional antibiotics often leads to resistance development as the majority of these antibiotics act on intracellular targets, leaving the bacterial morphology intact. Thus, they are highly prone to develop resistance through mutation. Much effort has been made to develop macromolecular antimicrobial agents that are less susceptible to resistance as they function by microbial membrane disruption. Antimicrobial hydrogels constitute an important class of macromolecular antimicrobial agents, which have been shown to be effective in preventing and treating multidrug-resistant infections. Advances in synthetic chemistry have made it possible to tailor molecular structure and functionality to impart broad-spectrum antimicrobial activity as well as predictable mechanical and rheological properties. This has significantly broadened the scope of potential applications that range from medical device and implant coating, sterilization, wound dressing, to antimicrobial creams for the prevention and treatment of multidrug-resistant infections. In this review, advances in both chemically and physically cross-linked natural and synthetic hydrogels possessing intrinsic antimicrobial properties or loaded with antibiotics, antimicrobial polymers/peptides and metal nanoparticles are highlighted. Relationships between physicochemical properties and antimicrobial activity/selectivity, and possible antimicrobial mechanisms of the hydrogels are discussed. Approaches to mitigating toxicity of metal nanoparticles that are encapsulated in hydrogels are reviewed. In addition, challenges and future perspectives in the development of safe and effective antimicrobial hydrogel systems especially involving co-delivery of antimicrobial polymers/peptides and conventional antimicrobial agents for eventual clinical applications are presented.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                20 December 2019
                January 2020
                : 12
                : 1
                : 8
                Affiliations
                Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø The Arctic University of Norway, Universitetsveien 57, 9037 Tromsø, Norway; selenia89.ternullo@ 123456gmail.com (S.T.); laura.v.schulte-werning@ 123456uit.no (L.V.S.W.); ann-mari.holsater@ 123456uit.no (A.M.H.)
                Author notes
                [* ]Correspondence: natasa.skalko-basnet@ 123456uit.no ; Tel.: +47-776-46640; Fax: +47-776-46151
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-0227-4171
                https://orcid.org/0000-0002-4301-2840
                Article
                pharmaceutics-12-00008
                10.3390/pharmaceutics12010008
                7022996
                31861794
                58d80a7e-475a-4560-b669-ab86edf8917e
                © 2019 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
                : 30 November 2019
                : 18 December 2019
                Categories
                Article

                curcumin,deformable liposomes,liposome surface charge,hydrogel,chitosan,wound therapy

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