Enhanced antinociceptive and anti-inflammatory effects of ibuprofen encapsulated in niosomal vesicles

The non-steroidal anti-inflammatory (NSAID) drug Ibuprofen (α-methyl-4-(2-methylpropyl)-benzeneacetic acid), is widely used in the treatment of pain, fever and inflammatory diseases. As far as its analgesic actions, ibuprofen inhibits the production of prostanoids, which mediate peripheral and central pain sensation, reducing the threshold to stimulation of nociceptors and increasing their terminal membrane excitability [1]. Niosomes, are unilamellar or multilamellar non-ionic surfactant vesicles. The main characteristic of these vesicles is their capability of encapsulating both lipophilic and hydrophilic drugs; hydrophilic drugs are encapsulated in the core of vesicles, while lipophilic drugs can be encapsulated into the lipophilic domain of the lipid bilayer [2]. In this work, we evaluated the analgesic activity of subcutaneous injection (s.c) of ibuprofen loaded TW20Gly niosomes (N-IBU), in comparison with free ibuprofen (IBU) in acute and chronic pain animal models. In vivo anti nociceptive activities of Ibuprofen-loaded vesicles were preliminarily tested by performing the writing and capsaicin screening assays. In writhing test, acetic acid as peripheral pain inducer was utilized. Analgesic activity was determined by entering the reduction of the number of writhes after acetic acid injection. In the early tested mice, a statistically significant reduction of writhes was observed only in IBU branch, whereas in the late tested mice the strongest reduction was observed in N[IBU] treated mice. In capsaicin experiments, in which mice were injected under the hind paw with capsacin, nociceptive activity was evaluated by measuring the time spent by mice in licking the injected paw. N-IBU significantly decreased capsaicin-induced paw licking, while IBU was ineffective. N-IBU also induced the strongest antinociceptive effects in Zymosan-induced hyperalgesia test. N-IBU increased pain threshold also in a model of neuropathic pain i.e. chronic sciatic nerve ligation, reducing hypealgesia and allodyia 2h after the treatment up to 4h. In the same conditions IBU did not gave any significant effect. We can conclude that the encapsulation of the drug into the niosomes significantly increases IBU analgesic activity, promoting a long lasting action of this drug. Thus, we propose TW20Gly niosomes as a new and more effective strategy to vehicle IBU to treat acute and chronic pain conditions. _____________________________________ 1. Brunton LL, Chabner BA, Knollman BC. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw- Hill Medical; 2011. 2. Di Marzio L, Marianecci C, Petrone M, Rinaldi F, Carafa M., Colloids Surf B Biointerfaces 2011, 82(1), 18.