Anti-inflammatory and anti-nociceptive activity of nanogels containing naproxen

Abstract

Although oral naproxen is an effective analgesic and anti-inflammatory, its use carries a risk of serious adverse effects, including gastrointestinal bleeding, ulceration and perforation. Therefore, the present work was aimed at developing pharmaceutically optimized topical nanogels of naproxen for treating musculoskelatal pain. Nanocapsules of naproxen were developed by adding the naproxen polymer solution to an aqueous solution containing stabilizer, using the emulsification evaporation technique. Nanogels were prepared by incorporating the nanocapsules of naproxen in the preformed gels. Stability of the nanogel dosage form was established at room temperature (25 deg C/60% RH) for 12 months and accelerated (40 deg C/75% RH) conditions stability for 6 months, as per the ICH guidelines. Anti-inflammatory and analgesic effects were studied in Wistar rats and Swiss mice. Anti-inflammatory effects were investigated using rat paw edema model, where Carrageenan was used as inflammation inducer. Rat paw volumes were measured with plethysmometer for 24 hours. The changes in paw volumes were compared with control and conventional gel. Analgesic effect was studied in mice by using the hot plate method. Latency to the heat stimulus for the gels was measured for 4 hours after application using the hot plate test, with a cut off time of 15 seconds. Increase in percentage of pain threshold was compared with control and conventional gel. The nanogel showed anti-inflammatory activity for more than twelve hours as compared to conventional gel and exhibited two-fold increase in pain threshold as compared to conventional gel, which showed activity for four hours. A pharmaceutically optimized clear, non-greasy and stable nanogel of naproxen for topical administration provided robust and long lasting antinociceptive effects, possibly through increased penetration with the use of nanocapsules as carriers. Human studies are needed to evaluate the clinical effects of the nanogel dosage forms. Supported by a grant from Relmada Therapeutics Inc.