Plant-derived natural products possess diverse pharmacological activities but their clinical translation is often limited by poor aqueous solubility, instability, low permeability, rapid clearance, and consequently low bioavailability. Mucoadhesive Drug Delivery Systems (MDDS) have emerged as a promising strategy to overcome these biopharmaceutical challenges by prolonging residence time at mucosal surfaces, enhancing absorption, enabling site-specific and controlled drug release, and improving therapeutic efficacy. This review provides a comprehensive overview of MDDS designed for plant-based natural products, covering fundamental mechanisms of mucoadhesion, types of mucoadhesive polymers, formulation approaches, routes of administration, and analytical strategies for characterization. Key delivery platforms including Nanoparticles (NPs), liposomes, lipid-polymer hybrid systems, hydrogels, microspheres, and mucoadhesive films are discussed in relation to their ability to enhance the pharmacokinetic and pharmacodynamic performance of phytochemicals. The review also summarizes current clinical trials, patented technologies, and commercially available products incorporating natural bioactives into mucoadhesive systems. Despite significant advances, challenges remain, including physicochemical variability of natural compounds, stability concerns, polymer selection, scale-up difficulties, and regulatory barriers. Emerging strategies such as thiolated polymers, stimuli-responsive systems, smart lipid-based carriers, advanced analytical tools, and AI-assisted formulation design offer new opportunities to further optimize MDDS for natural products. Overall, MDDS represent a versatile and translational platform capable of unlocking the therapeutic potential of phytochemicals and facilitating their progression from bench to clinical application.
Zahra et al. (Mon,) studied this question.