Antinociceptive effects of Curcumin-loaded PLGA vesicles

Curcumin is yellow polyphenol, extracted from the rhizomes of turmeric (Curcuma longa) and used in traditional medicine for many centuries in countries such as India and China (1). Curcumin demonstrated a wide range of pharmacological activities that include antitumor, anti-amyloid, antioxidant, anti-inflammatory properties and analgesia. At present, no data are reported in the literature on the antinociceptive effects induced by curcumin loaded in PLGA vesicles (PLGA-CURC) and we investigated first the effects of PLGA-CURC in acute models of pain after systemic and central administration. Male CD-1 mice (Harlan, Italy) weighing 25-30 g were used for all experiments. The research protocol was authorized by the Italian Ministry of Health, according to Legislative Decree 26/14. Subcutaneous injection of a dilute solution of formalin (1%, 20 μl/paw) into the mice hind paw evokes nociceptive behavioral responses, such as licking, biting the injected paw or both, which are considered indices of nociception (2). The nociceptive response shows a biphasic trend, consisting of an early phase occurring from 0 to 10 min after the formalin injection, due to the direct stimulation of peripheral nociceptors, followed by a late prolonged phase occurring from 15 to 40 min, that reflects the response to inflammatory pain. The total time (s) that the animal spent licking or biting its paw during the formalin-induced early and late phase of nociception was recorded. In the first series of experiments curcumin-vehicle, curcumin, blank-PLGA and curcumin-PLGA (0.045 mg curcumin/mg of nanoparticles, a generous gift of dr. A. Ranjan, University of North Texas Health Science Center, Fort Worth, TX, USA) were administered i.v. at the dose of 20 mg/kg, in curcumin. In the second series of experiments curcumin-vehicle, curcumin, blank-PLGA and curcumin-PLGA were administered i.t. at doses of 5 and 25 g/mouse, in curcumin. The significance among the groups (P<0.05) was evaluated with ANOVA followed by Tukey’s post-hoc comparisons using GraphPad Prism 6.03 software. After i.v. treatment, ANOVA revealed no difference between groups in the early phase of the formalin test. On the contrary, in the late phase of the test i.v. curcumin-PLGA was able to strongly reduced the nociceptive behavior induced by formalin. After i.t. administration at the dose of 5 g/mouse, treatments did not change licking behavior induced by formalin neither in the early nor in the late phase of the test. After i.t. administration at the dose of 25 g/mouse, curcumin-PLGA was able to reduce licking activity - in confront to curcumin-vehicle and blank-PLGA treated animals - both in the early and in the late phase of the test. These data suggest that curcumin-PLGA may be developed as a medicine to treat pain, by warranting further rigorously conducted studies to define the long-term efficacy and safety. 1. P. Anand, S.G. Thomas, A.B. Kunnumakkara, C. Sundaram, K.B. Harikumar, B.Sung, S.T.Tharakan, K. Misra, I.K. Priyadarsini, K.N. Rajasekharan, B.B. Aggarwal, Biochem. Pharmacol. 2008, 76, 1590. 2. M. Colucci, F. Maione, M.C. Bonito, A. Piscopo, A. Di Giannuario, S. Pieretti, Pharmacol Res., 2008, 57, 419.