Purpose: Diclofenac sodium is a non-steroidal anti-inflammatory drug with anti-inflammatory, anti-rheumatic, analgesic, antipyretic effects, which widely used for osteoarthritis, rheumatoid arthritis, a variety of fever and pain relief. Oral and external application are the most common administration forms, the former has a strong gastrointestinal adverse reaction and first-pass elimination effect, and the latter has a low bioavailability due to the barrier function of the stratum corneum. Dissolving microneedle patch (DMNP) are prepared from dissolvable and biocompatible polymeric materials with sufficient mechanical properties to cross the barrier of the stratum corneum, avoid the first-pass elimination effect and reduce adverse drug reactions. In this study, diclofenac sodium was loaded in dissolving microneedle patches (DS-DMNPs) to investigate the analgesic effect induced by glacial acetic acid-induced acute inflammation in SD rats.
Methods: The DS-DMNPs were prepared by a two-step molding process developed in our previous research which can keep DS in the tip of microneedles. The sharps of obtained microneedles were observed and measured by optical microscopy.
Forty nine SD rats were divided into 7 groups randomly: Group A (external application of saline); Group B (Blank dissolving microneedle patches, B-DMNPs, no DS); Group C (external application of Voltaren Emulgel, 1 mg DS); Group D (intragastric administration, 4 mg DS); Group E (low-dose DS-DMNPs, 150 μg DS); Group F (medium-dose DS-DMNPs, 300 μg DS) and Group G (high-dose DS-DMNPs, 600 μg DS). DMNPs were applied on the inner ear pinna with thumb and secured onto ear with 3MTM Bandaging Tape for 30 min. Then each rat was intraperitoneally injected (i.p.) with 2 mL of 1% glacial acetic acid solution and the torsion times were recorded in 2 hours. Statistical analysis was carried out using SPSS 16.0.
Results: The prepared DS-DMNPs showed a cone sharp about 800 μm in height and 300 μm in base diameter (Fig.1).
Rats administrated with saline and B-DMNPs had most frequent torsion, the average total torsion times in 2 hours was about 70 for both group. Torsional frequency decreased significantly in the other 5 groups with drug administrated, which showed the analgesic effect of Diclofenac sodium. External application of Voltaren Emulgel played a similar analgesic effect with the low-dose DS-DMNPs. However, the dosage of the former was 6 times more than the latter. Compared with high-dose DS-DMNPs, intragastric administrated with 6.7 times dosage of Diclofenac sodium can play the same analgesic effect, which also indicated the extremely advantage of the DS-DMNPs. In the DS-DMNPs groups, total torsion times decreased correspondingly with the increase in dose, showing a dose-dependent pattern.(Fig. 2)
Conclusion: Diclofenac sodium loaded in DMNPs was able to play much stronger analgesic effect compared with oral and external application in the treatment of acute inflammation which induced by glacial acetic acid-induced acute inflammation in SD rats. DMNPs will play an immeasurable role in the treatment of arthritis.
Minglong Chen– Bengbu medical college
Yingmei Wei– Bengbu Medical College
Hao Liu– Bengbu Medical College
Min Li– Bengbu Medical College
Zhiyong Dong– Bengbu Medical College
Yingying Li– Bengbu Medical college