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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.

Knowledge of the mechanism of action of skin penetration enhancers is essential to formulators for optimizing formulations and to maximize the efficacy of enhancers. To obtain information about the effects of penetration enhancers as a fast initial screening, investigations have been performed to identify possible correlations of the biological effectiveness of penetration enhancers with their interaction with a well-defined model system consisting of skin mimic lipid bilayers, as determined by calcein release experiments using stratum corneum lipid liposomes (SCLLs). We aimed to investigate the enhancing effects of different concentrations of two chemical penetration enhancers, Kolliphor RH40 and Transcutol on SCLLs. The results obtained by SCLL-based techniques were compared with conventional ex vivo penetration studies in case of Kolliphor RH40 to evaluate the potential of SCLLs as an alternative tool for screening various types and concentrations of penetration enhancers. As a result, calcein leakage assay performed with SCLL was considered to be a good model for the skin penetration enhancing effect. This method could be used as a time-saving and sensitive alternative in vitro screening technique in the early stage of the development of dermal formulations.