In situ gel-forming oil solubilizing alpha-lipoic acid as a physical shielding alleviated chemotherapy-induced oral mucositis via inhibiting oxidative stress.

Oral mucositis (OM) is a common and serious complication of cancer chemoradiotherapy. OM managements mainly focused on topical healthcare or analgesia, which offers limited wound healing. Herein, in situ gel-forming oil (LGF) have been developed as a physical shielding for OM treatment. LGF oil, composed of soybean phosphatidyl choline (40 %, w/w), glycerol dioleate (54 %, w/w), and alcohols (6 %, w/w), is a viscous oil-like liquid. The contact angle of LGF oil on porcine buccal mucosa were 30 degrees , significantly smaller than that of water (60 degrees ), indicating its good wetting and spreading properties. Besides, the adhesion force and adhesion energy of LGF oil toward porcine buccal mucosa was as high as 3.9 +/- 0.2 N and 60 +/- 2 J/m(2), respectively, indicating its good adhesive property. Moreover, the hydrophobic alpha-lipoic acid (LA) as a native antioxidative agent was highly solubilized in LGF oil, its solubility in which was above 100 mg/mL. Upon contacting with saliva, LA-loaded LGF oil (LA-LGF) could rapidly transform from oil into gel that adheres on oral mucosa. Moreover, LA was slowly released from the formed LA-LGF gel, which benefited alleviating oxidative stress caused by chemoradiotherapy. In vivo animal experiments showed that LA-LGF could effectively promote the repairing of oral mucosa wound of 5-fluorouracil induced OM rats. Besides, the mucosa edema was greatly improved and new granulation around wound was produced after LA-LGF treatment. Meanwhile, the production of proinflammatory cytokines such as IL-1beta, TNF-alpha, 1L-6 was substantially inhibited by LA-LGF. Collectively, LGF oil as carrier of hydrophobic drug might be a promising strategy for oral mucositis.