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

• Published in: International journal of pharmaceutics 2024-11, Vol.665, p.124714, Article 124714
• Main Authors: Zhang, Yingying, Jiang, Zhijiang, Lu, Kaili, Ding, Bingyu, Wang, Jie, Wang, Neili, Li, Dingwei, Yu, Fengnan, Zhang, Mengjiao, Xu, Helin
• Format: Article
• Language: English
• Subjects: In situ gel-forming; Oil; Oral mucositis
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124714

[Display omitted] 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°, significantly smaller than that of water (60°), 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/m2, respectively, indicating its good adhesive property. Moreover, the hydrophobic α-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-1β, TNF-α, 1L-6 was substantially inhibited by LA-LGF. Collectively, LGF oil as carrier of hydrophobic drug might be a promising strategy for oral mucositis.