DICLOFENAC SODIUM ENTRAPPED IN MICROPARTICLES EXHIBIT PROLONGED ANTINOCICEPTIVE EFFECTS IN HOT PLATE TEST IN RATS
We aimed to evaluate the influence of microparticles containing DCF on the somatic nociceptive reactivity in rats. Material and methods: We used a novel procedure to entrap DCF in soft matter vesicles based on phosphatidylcholine and coated with chitosan. These original carrier systems were physicochemical characterized using a Malvern Zetasizer Nano ZS, ZEN-3500 apparatus. To investigate the effects of microparticles with DCF on the nociceptive reactivity, 3 identical groups of 5 white male Wistar rats each were used. The substances were administered orally (using an eso-gastric device) in a single dose according to the following protocol: Group 1 (Control): distilled water 0.3 ml/100 g body weight - control; Group 2 (DCF): 5 mg/kg body weight diclofenac; Group 3 (DCF-mp): chitosan-based microparticles entrapping diclofenac 5 mg/kg body weight. The somatic nociceptive reactivity was estimated using the hot plate model. The latency time reaction to paws noxious thermal stimulation was assessed before the experiment (baseline) and 15, 30, 60, 90, 120 minutes, 4, 6, 8, 10 hours, after the substances administration. Experimental protocol was approved, and the research were performed according to recommendations of the “Grigore T. Popa” University of Medicine and Pharmacy Committee for Research and Ethical Issues. The data were presented as +/- standard deviation and analyzed using SPSS for Windows version 17.0 and ANOVA one-way method. Results: We prepared original microparticles containing DCF of 562 ± 13.37 nm mean size, +45 ± 1.67 mV mean Zeta potential with a good stability in colloidal solution. The treatment with DCF resulted in substantial increase of the latency response, in the interval between 15 minutes and 90 minutes in hot plate test. In use of DCF-mp resulted in statistically significant increase of the latency time, between 2 and 10 hours in this somatic pain model in rats. Conclusions: The lipid vesicles stabilized with chitosan, as carrier for DCF, presented the advantage of a prolonged release of active substance, comparing with non-entrapped drug in hot plate model in rats.
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