Saliva-Mediated Muco-Adhesive Drug Delivery Systems: A Systematic Review of Polymeric Films and Nanoparticle-Based Approaches

Background: Muco-adhesive drug delivery systems utilizing saliva as a physiological medium have gained attention for enhancing drug retention, bioavailability, and patient compliance in oral cavity applications. The physicochemical properties of saliva comprising mucins, enzymes, and electrolytes play a critical role in determining the adhesion, stability, and release behavior of polymer-based drug delivery systems. This systematic study aimed to evaluate the influence of salivary interaction on the performance of muco-adhesive polymeric films and nanoparticles, focusing on their adhesion strength, stability, and controlled drug release characteristics. Methods: A comprehensive literature search was conducted across PubMed, Scopus, and ScienceDirect for studies published between 2010 and 2025, focusing on polymeric muco-adhesive delivery systems tested under simulated or in vivo salivary conditions. Studies assessing physicochemical parameters such as muco-adhesive strength, drug release kinetics, and polymer–saliva interactions were included. Data extraction and synthesis followed the PRISMA 2020 guidelines. Results: Across the included studies, chitosan-based nanoparticles demonstrated superior muco-adhesive strength (adhesion times up to 6 hours) and enhanced mucosal permeation compared to synthetic polymers. HPMC–PVP films maintained prolonged contact time and consistent drug release under salivary enzymatic conditions, whereas carbopol-based systems showed variable stability due to pH and enzymatic degradation. Both polymeric films and nanoparticles exhibited improved therapeutic efficacy and patient tolerability when optimized for salivary compatibility. Conclusion: The findings underscore the importance of tailoring polymer composition and molecular interactions to salivary conditions for achieving efficient muco-adhesive performance. Integrating salivary environment simulations into formulation development can significantly enhance the clinical translation of buccal and sublingual drug delivery systems. Future research should emphasize hybrid polymer-nanoparticle matrices and in vivo correlation studies to refine saliva-mediated muco-adhesive delivery technologies.