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      Electroporation-enhanced transdermal diclofenac sodium delivery into the knee joint in a rat model of acute arthritis

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          Since electroporation (EP) can increase the permeability of biological membranes, we hypothesized that it offers an opportunity to enhance the transdermal delivery of drugs for intra-articular indications. Our aim was to compare the anti-inflammatory and analgesic efficacy of EP-combined topical administration of diclofenac sodium hydrogel (50 mg mL −1 in 230 µL volume) with that of an equivalent dose of oral (75 mg kg −1) and simple topical administration.


          Arthritis was induced with the injection of 2% λ-carrageenan and 4% kaolin into the right knee joints of male Sprague Dawley rats. EP was applied for 8 min with 900 V high-voltage pulses for 5 ms followed by a 20 ms break. Drug penetration into the synovial fluid and plasma was detected by high-performance liquid chromatography. Leukocyte–endothelial interactions were visualized by intravital videomicroscopy on the internal surface of the synovium. Inflammation-induced thermal and mechanical hyperalgesia reactions, knee joint edema, and inflammatory enzyme activities were assessed at 24 and 48 h after arthritis induction.


          EP significantly increased the plasma level of diclofenac as compared with the topical controls 10 min after the 2% λ-carrageenan and 4% kaolin injection. Increased leukocyte–endothelial interactions were accompanied by joint inflammation, which was significantly reduced by oral and EP diclofenac (by 45% and by 30%, respectively) and only slightly ameliorated by simple topical diclofenac treatment (by 18%). The arthritis-related secondary hyperalgesic reactions were significantly ameliorated by oral and EP-enhanced topical diclofenac treatments. The knee cross-section area (which increased by 35%) was also reduced with both approaches. However, simple topical application did not influence the development of joint edema and secondary hyperalgesia.


          The study provides evidence for the first time of the potent anti-inflammatory and analgesic effects of EP-enhanced topical diclofenac during arthritis. The therapeutic benefit provided by EP is comparable with that of oral diclofenac; EP is a useful alternative to conventional routes of administration.

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          Most cited references 50

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          Theory of electroporation: A review

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            The prevalence and burden of arthritis.

            The prevalence of arthritis is high, with osteoarthritis (OA) being one of the most frequent disorders in the population. In England and Wales, between 1.3 and 1.75 million people have OA and a further 0.25-0.5 million have rheumatoid arthritis (RA), while in France some 6 million new diagnoses of OA are made each year. In 1997, approximately 16% of the US population had some form of arthritis. This prevalence is expected to increase in the coming years, as arthritis more often affects the elderly, a proportion of the population that is increasing. The economic burden of such musculoskeletal diseases is also high, accounting for up to 1-2.5% of the gross national product of western nations. This burden comprises both the direct costs of medical interventions and indirect costs, such as premature mortality and chronic and short-term disability. The impact of arthritis on quality of life is of particular importance. Musculoskeletal disorders are associated with some of the poorest quality-of-life issues, particularly in terms of bodily pain (mean score from the MOS 36-item Short Form Health Survey of 52.1) and physical functioning (49.9), where quality of life is lower than that for gastrointestinal conditions (bodily pain 52.9, physical functioning 55.4), chronic respiratory diseases (72.7, 65.4) and cardiovascular conditions (64.7, 59.3).
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              The pathogenesis and prevention of joint damage in rheumatoid arthritis: advances from synovial biopsy and tissue analysis.


                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                27 June 2018
                : 12
                : 1917-1930
                [1 ]Institute of Surgical Research, University of Szeged, Szeged, Hungary, hartmann.petra@ 123456med.u-szeged.hu
                [2 ]Department of Traumatology, University of Szeged, Szeged, Hungary
                [3 ]Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary
                [4 ]Department of Pathology, University of Szeged, Szeged, Hungary
                [5 ]Department of Physiology, University of Szeged, Szeged, Hungary
                Author notes
                Correspondence: Petra Hartmann, Institute of Surgical Research, University of Szeged, Szőkefalvi-Nagy B. u. 6, H-6720 Szeged, Hungary, Tel +36 62 545 103, Fax +36 62 545 743, Email hartmann.petra@ 123456med.u-szeged.hu
                © 2018 Hartmann et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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