Electroporation-enhanced transdermal diclofenac sodium delivery into the knee joint in a rat model of acute arthritis
Purpose: 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 to...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2018
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| Sorozat: | DRUG DESIGN DEVELOPMENT AND THERAPY
12 |
| doi: | 10.2147/DDDT.S161703 |
| mtmt: | 3394721 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/13810 |
| Tartalmi kivonat: | Purpose: 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 microL volume) with that of an equivalent dose of oral (75 mg kg(-1)) and simple topical administration. Methods: Arthritis was induced with the injection of 2% lambda-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. Results: EP significantly increased the plasma level of diclofenac as compared with the topical controls 10 min after the 2% lambda-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. Conclusion: 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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| Terjedelem/Fizikai jellemzők: | 1917-1930 |
| ISSN: | 1177-8881 |