Nanotechnology-Based Drug Delivery Approaches of Mangiferin: Promises, Reality and Challenges in Cancer Chemotherapy

SIMPLE SUMMARY: The current review describes mangiferin (MGF), a secondary plant metabolite of a xanthone derivative obtained from mango plants and known for its therapeutic activities. It is potent against various cancers, including breast, liver, prostate and glioblastoma, by inhibiting lipid peroxidation and preventing NFκB activation. However, MGF faces challenges such as poor lipophilicity, high first-pass metabolism and extensive P-gp efflux. Nano-drug delivery and deep learning-based approaches are being explored to overcome these challenges. Clinical trials and patents are ongoing, and MGF is expected to become a promising therapeutic biological molecule for cancer treatment. ABSTRACT: Mangiferin (MGF), a xanthone derived from Mangifera indica L., initially employed as a nutraceutical, is now being explored extensively for its anticancer potential. Scientists across the globe have explored this bioactive for managing a variety of cancers using validated in vitro and in vivo models. The in vitro anticancer potential of this biomolecule on well-established breast cancer cell lines such as MDA-MB-23, BEAS-2B cells and MCF-7 is closer to many approved synthetic anticancer agents. However, the solubility and bioavailability of this xanthone are the main challenges, and its oral bioavailability is reported to be less than 2%, and its aqueous solubility is also 0.111 mg/mL. Nano-drug delivery systems have attempted to deliver the drugs at the desired site at a desired rate in desired amounts. Many researchers have explored various nanotechnology-based approaches to provide effective and safe delivery of mangiferin for cancer therapy. Nanoparticles were used as carriers to encapsulate mangiferin, protecting it from degradation and facilitating its delivery to cancer cells. They have attempted to enhance the bioavailability, safety and efficacy of this very bioactive using drug delivery approaches. The present review focuses on the origin and structure elucidation of mangiferin and its derivatives and the benefits of this bioactive. The review also offers insight into the delivery-related challenges of mangiferin and its applications in nanosized forms against cancer. The use of a relatively new deep-learning approach to solve the pharmacokinetic issues of this bioactive has also been discussed. The review also critically analyzes the future hope for mangiferin as a therapeutic agent for cancer management.