Mucoadhesive Phenolic Pectin Hydrogels for Saliva Substitute and Oral Patch

Abstract

Oral disease is one of the most common conditions worldwide, negatively affecting general health, reducing the quality of life, and often developing into systemic illness. However, the design of therapeutic agents for oral diseases is challenging due to various unique features of the oral cavity, including its wet and dynamic environment and curved shape. Herein, the development of highly biocompatible mucoadhesive functional hydrogels for oral applications is reported, generated by introducing bio‐inspired phenolic moieties into a pectin polymer. Pyrogallol‐functionalized pectin (Pec‐PG) can be crosslinked in situ via autoxidation without chemical agents and readily fabricated as various formulations. Sprayable Pec‐PG hydrogel exhibits strong mucoadhesion and outstanding hydration ability ex vivo and in vivo, thus displaying significant potential as a novel saliva substitute for dry mouth. The authors further show that topical application of mucoadhesive Pec‐PG patches pre‐loaded with corticosteroid significantly promotes the repair of diabetic oral ulcer tissue via prolonged drug release, free radical scavenging, and physical barrier effects. Moreover, similar applications for oral ulcer treatment using a pectin hydrogel modified with catechol (Pec‐CA), another phenolic moiety are demonstrated. Together, these findings suggest that mucoadhesive phenolic pectin derivatives can provide highly biocompatible, convenient, and effective hydrogel platforms for treating oral diseases.

A double-layer thin oral film for wet oral mucosa adhesion and efficient treatment of oral ulcers

“…Mucin, the main component of mucus, is produced by epithelial tissue and secreted onto the mucosal surface to preserve a healthy oral environment. 15,18 So, the adhesion mechanism of the C-P-G film was elucidated by investigating the interaction of C-P-G with mucin. The results of atomic force microscopy (AFM), the average surface roughness (Ra), and dynamic light scattering (DLS) revealed that aggregates formed when mucin co-mingled with C-P-G, suggesting a high affinity between C-P-G and mucin (Fig.…”

“…Despite widespread exploration of mussel-inspired formulations for strong adhesion in wet environments, 15,34 they often bring about instability due to the introduction of unstable compounds, organic solvents, and toxic cross-linking agents. These factors contribute to unpredictable safety issues, limiting their clinical translation.…”

“…14 However, due to biosafety limitations, discomfort, and impaired in situ drug delivery caused by toxic cross-linking agents, organic solvents, complex systems, and a thick appearance, these formulations face obstacles in clinical translation. 14,15 Therefore, there is an urgent need to develop a formulation suitable for topical administration to the oral mucosa for efficient OU treatment. What are the characteristics of an ideal oral mucosal topical drug delivery system (DDS)?…”

Emerging polymeric materials for treatment of oral diseases: design strategy towards a unique oral environment

“…To achieve this goal, Seung-Woo Cho et al employed pyrogallol in pectin polymers to construct mucoadhesive polymer hydrogels. 129 Mucoadhesive strength was achieved by covalent bonding including Michael addition and Schiff reactions, and non-covalent interactions including hydrogen bonding, hydrophobic interactions and π–π stacking between pyrogallol and mucin proteins. After spraying onto a rat tongue, hydrogels formed in situ and adhered onto the tongue tightly regardless of vigorous PBS wash.…”

Pectin hydrogels for controlled drug release: Recent developments and future prospects

“…Pectin hydrogels find valuable pharmaceutical applications owing to their biocompatibility, controlled drug release capabilities ( Güner et al, 2021 ), and versatility in formulation. These hydrogels are employed in oral drug delivery systems ( Choi et al, 2023 ), where they protect sensitive drugs from the harsh gastric environment and enable controlled release in the intestinal tract, enhancing drug bioavailability and patient compliance. In addition, pectin hydrogels are used for targeted and sustained drug delivery to specific sites ( An et al, 2021 ), rendering them suitable for treating various ailments, including gastrointestinal disorders and chronic diseases.…”