Targeted-Produced Dirhamnolipids from Pseudomonas aeruginosa Induce Antinociception in Mice.

Rhamnolipids are highly effective surface-active glycolipid biosurfactants with enormous market potential. Composed of β-d-(β-d-hydroxyalkanoyloxy)-alkanoic acids attached to mono- or dirhamnose moieties, these green amphiphilic molecules exhibit remarkable biomedical prospects, with the double rhamnose congeners being the most effective ones. Although reports on dirhamnolipid antimicrobial activities and wound healing properties are quite abundant, the antinociceptive effect on inflammatory pain has never been tested before. Here we report a targeted-producing dirhamnolipid process, which reaches 95.1% of dirhamnolipid abundance, followed by a single-step purification procedure through a homemade silica cartridge, achieving highly pure glycolipid (99.0% rhamnolipids and 97.5% dirhamnolipids). Purified Di-RL (pDi-RL) therapeutic effects were investigated in murine models of pain and inflammation induced by carrageenan, acetic acid, and formalin. Mice were pretreated with pDi-RL at doses of 0.3 and 3 mg/kg, subcutaneously, 30 min before the inflammatory stimulation. pDi-RL at the 3 mg/kg dose reduced the mechanical sensitivity and leukocyte infiltrate in the cutaneous plantar skin induced by carrageenan and overt pain-like behaviors induced by formalin and acetic acid. Furthermore, the pDi-RL mechanisms were assessed in a peritonitis model induced by carrageenan, and pDi-RL reduced the total leukocyte recruitment (mononuclear and polymorphonuclear cells) and superoxide anion production by recruiting leukocytes in the peritoneal exudate. Here, we demonstrate for the first time the antinociceptive activity of Di-RL and, at least in part, its mechanism in murine models of pain and inflammation.