Glycyrrhizin loaded hyaluronic acid nanofiber-based artificial saliva for the management of oral mucositis: Preparation, optimization and in-vitro evaluation

Oral cancer patients receiving chemotherapy/radiotherapy experience oral mucositis (OM), a condition believed to significantly impact the quality of life and treatment outcome. Artificial saliva offers a promising alternative for managing chemotherapy-induced OM. Here we aimed to design and optimize multifunctional Glycyrrhizinloaded Hyaluronic acid (HA) nanofiber-based artificial saliva to effectively manage chemotherapy-induced OM with aided benefits against inflammatory, infectious conditions. Nanofiber was prepared by electrospinning technique and optimized using a Quality-by-Design (QbD) approach employing Box-Behnken Design. Identified critical material attribute (CMA) was polymer concentration (X1), and critical process parameters (CPP) were flow rate (X2) and applied voltage (X3). Nanofiber was characterized for morphology, moisture retention capacity, deviation in content uniformity, and drug entrapment efficiency and evaluated based on drug release profile, wettability, degree of swelling, tensile strength, antioxidant, antimicrobial, anti-inflammatory potential, cytotoxicity and chemoprotective activities against selective cell lines to establish their therapeutic potential. The fibers' diameter was 207.6 & PLUSMN; 1.36 nm with 696.66 & PLUSMN; 21.11% moisture retention capacity and 4.36 & PLUSMN; 0.04% deviation in content uniformity. Fibers with immensely high wettability and moisturizing efficacy (86.16%) pose their tremendous utility as artificial saliva. Provided with good antioxidant and antimicrobial potential, these Glycyrrhizin-loaded fibers decreased pro-inflammatory cytokines levels in RAW 264.7 macrophages while maintaining high (83%) cellular viability in 5-Fluorouracil (5-FU) treated healthy cells, ensuring its noteworthy chemo-protective effect. These findings strengthen the views that HA and Glycyrrhizin help in cell regeneration and protection. Provided with good storage stability, the developed nanofiber-based system proves their fate in meeting all the pharmaceutical and pharmacological standards considered in managing OM, being a potential candidate against chemotherapy-induced mucositis.

Automated summary

By designing and optimizing a multifunctional Glycyrrhizin-loaded Hyaluronic acid (HA) nanofiber-based artificial saliva, this study aims to effectively manage chemotherapy-induced oral mucositis (OM) while providing benefits against inflammatory and infectious conditions.