Bridging bioactive metabolites of Phoenix dactylifera L. with advanced nanocarrier technologies for mucoadhesive drug...

Phoenix dactylifera L. (PD), a monocotyledonous flowering plant from the Arecaceae family, is one of fourteen species in the Phoenix genus and has been cultivated in the Middle East for over 6,000 years. Its fruit is regarded as a complete food due to its rich nutritional and medicinal profile, containing flavonoids, carotenoids, procyanidins, phenolics, sterols, anthocyanins, steroids, fatty acids, proteins, and amino acids. These bioactive metabolites contribute to its therapeutic potential, particularly in anticancer applications. To enhance the effectiveness of such natural metabolites in medical treatments, Nano-Drug Delivery Systems (NDDS) have gained significant attention, offering controlled drug release, increased permeability and retention, prolonged circulation time, and reduced degradation. This review employed a comprehensive literature search across databases such as Web of Science, PubMed, Google Scholar, and Scopus, using keywords like "Phoenix dactylifera," "date palm," "Ajwa," "natural products," "NDDS," and "Drug Delivery System," focusing on relevant publications from January 1995 to May 2025. It provides a comprehensive up-to-date overview of the pharmacological properties of PD metabolites and explores various innovative NDDS formulations including phytosomes, liposomes, microspheres, ethosomes, solid lipid nanoparticles, niosomes, proniosomes, dendrimers, and liquid crystals as potential strategies to improve the delivery and efficacy of PD-based therapies. Additionally, the review discusses the advantages and limitations of these delivery systems in the context of developing PD bioactives as a viable anticancer agent.