Antibacterial, anti-inflammatory and wet-adhesive poly(ionic liquid)-based oral patch for the treatment of oral ulcers with bacterial infection

Oral aphthous ulcers are a common inflammatory efflorescence of oral mucosa, presenting as inflammation and oral mucosal damage and manifesting as pain. The moist and highly dynamic environment of the oral cavity makes the local treatment of oral aphthous ulcers challenging. Herein, a poly(ionic liquid)-based diclofenac sodium (DS)-loaded (PIL-DS) buccal tissue adhesive patch fabricated with intrinsically antimicrobial, highly wet environment adhesive properties and anti-inflammatory activities to treat oral aphthous ulcers was developed. The PIL-DS patch was prepared via polymerization of a catechol-containing ionic liquid, acrylic acid, and butyl acrylate, followed by anion exchange with DS-. The PIL-DS can adhere to wet tissues, including mucosa muscles and organs, and efficiently deliver the carried DS- at wound sites, exerting remarkable synergistic antimicrobial (bacteria and fungi) properties. Accordingly, the PIL-DS elicited dual therapeutic effects on oral aphthous ulcers with Staphylococcus aureus infection through antibacterial and anti-inflammatory activities, significantly accelerating oral aphthous ulcer healing as an oral mucosa patch. The results indicated that the PIL-DS patch, with inherently antimicrobial and wet adhesion properties, is promising for treating oral aphthous ulcers in clinical practice. STATEMENT OF SIGNIFICANCE: Oral aphthous ulcers are a common oral mucosal disease, which could lead to bacterial infection and inflammation in severe cases, especially for people with large ulcers or low immunity. However, moist oral mucosa and highly dynamic oral environment make it challenging to maintain therapeutic agents and physical barriers at the wound surface. Therefore, an innovative drug carrier with wet adhesion is urgently needed. Herein, a poly(ionic liquid)-based diclofenac sodium (DS)-loaded (PIL-DS) buccal tissue adhesive patch was developed to treat oral aphthous ulcers showing intrinsically antimicrobial and highly wet environment adhesive properties due to the presence of catechol-containing ionic liquid monomer. Additionally, the PIL-DS showed significantly therapeutic effects on oral aphthous ulcers with S. aureus infection through antibacterial and anti-inflammatory activities. We expect that our work can provide inspiration for the development of treatment for microbially infected oral ulcers.