PurposeSince 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.MethodsArthritis 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.ResultsEP 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.ConclusionThe 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.
Background The potential advantages of hydroxyapatite (HA)-coated cementless total knee arthroplasty (TKA) implants are bone stock preservation and biological fixation. Studies comparing the outcomes of HA-coated cementless, non HA-coated cementless (uncemented) and cemented TKA implants reported contradictory data. Our aim was to provide a comparison of the effects of HA coating of tibial stem on the stability and functionality of TKA implants. Methods A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the CENTRAL databases up to May 31st, 2019. The primary outcome was Maximum Total Point Motion (MTPM) of the tibial stem. This parameter is determined by radiosterometric analysis and refers to the migration pattern of the prosthesis stems. The clinical outcomes of the implanted joints were evaluated by the Knee Society Knee Score (KSS) and the Knee Society Function Score (KFS). Weighted mean difference (WMD) with 95% confidence interval (CI) were calculated with the random-effects model. Results Altogether, 11 randomized controlled trials (RCTs) with 902 patients for primary TKA implants were included. There was a statistically significant difference in the MTPM values with the use of HA-coated and uncoated uncemented implants (WMD = +0.28, CI: +0.01 to +0.56, P<0.001). However, HA-coated stems showed significantly higher migration when compared with the cemented prostheses (WMD =-0.29, CI:-0.41 to-0.16, P<0.001). The KSS values of HA-coated implants were significantly higher than those for the uncemented PLOS ONE
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