Synthesis and Characterization of Highly-Stable Mucoadhesive Gel for Oral Drug Delivery

Fatima Shahid¹Hashmat Gul^1*Muhammad Amber Fareed^2,3*Faheem Ullah^4,5*Humayoon Shafique Satti⁶Muhammad Kaleem¹

• ¹Department of Dental Materials - Army Medical College – National University of Medical Sciences, Rawalpindi, Pakistan
• ²Clinical Sciences Department, College of Dentistry, Ajman University, Ajman, United Arab Emirates
• ³Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
• ⁴Department of Biological Sciences - National University of Medical Sciences (NUMS), Rawalpindi, Pakistan
• ⁵Bioresource Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Gelugor, Pulau Penang, Malaysia
• ⁶Department of Bioinformatics, National University of Medical Sciences, Rawalpindi, Pakistan

Objectives: The aim of this study is to synthesize and characterize a novel mucoadhesive hydrogel for oral drug delivery, predominantly to treat oral ulcers. Exosomes derived from mesenchymal stem cells are incorporated in the hydrogel with the intention to increase the therapeutic effects and to minimize risks such as drug resistance and secondary infections. Methods: Basic hydrogel was synthesized via a combination of hyaluronic acid and carbomer. Additionally, various anti-microbial agents were added to produce hydrogel variants. Exosomes were incorporated in the hydrogels to create a system for drug delivery. Scanning electron microscopy (SEM)f, Fourier-transform infrared spectroscopy (FTIR), rheological analysis and mucoadhesive testing, swelling and degradation analysis at different pH levels were carried out to characterize the hydrogel. In-vitro testing of the basic composition and variant hydrogels were then carried out which included determination of antimicrobial properties against Escherichia coli, Streptococcus aureus and Candida albicans, cytocompatibility analysis via WST-8 fibroblasts with fibroblasts quantification assay, exosomes release kinetics via UV-vis spectrophotometry. Results: SEM analysis revealed porous and interconnected structure within the hydrogel matrix which is essential for loading drugs. FTIR spectrum's characteristic peaks confirmed the presence of the constituent polymers. Hydrogel exhibited suitable viscoelastic properties, strong mucoadhesion on bovine mucosa and satisfactory swelling and degradation properties at various pH levels. Effective antimicrobial activity against E. coli, S. aureus and Candida albicans was observed in the study groups in addition to cytocompatibility and increase in exosome release from hydrogel with time. Conclusion: The study determines that the exosome-loaded mucoadhesive hydrogel can be used as a promising alternative to traditional oral ulcer treatments. The viscoelastic and mucoadhesive behavior along with antimicrobial activity and biocompatible nature suggests that the synthesized hydrogel addresses the challenges faced with conventional oral ulcer treatment.