A holistic review on zein nanoparticles and their use in phytochemicals delivery

In the quest for effective yet safe treatments, researchers from the pharmaceutical and medical field have directed their attention towards active pharmaceutical ingredients (APIs) derived from plant sources known as "Phytochemicals" as an alternative to synthetic APIs. Many phytochemicals exhibit diverse pharmacological actions stemming from their anti-inflammatory and antioxidant properties with negligible side effects. Nevertheless, conventional phytochemicals drug delivery systems have failed to protect and specifically deliver their cargo to the target site. Troublesome drugs are better delivered via their encapsulation in nanoparticles (NPs) that can effectively overcome such shortcomings. Zein is a biodegradable, biocompatible FDA-approved plant protein easily formulated into NPs. Generally, zein nanoparticles (ZNPs) have a considerably small particle size and a hydrophobic core that can accommodate and protect high amounts of poorly water-soluble drugs and sustain their release, making ZNPs an optimum carrier for phytochemicals. This review provides an overview on ZNPs and their use in phytochemicals drug delivery. It focuses on the plethora of different designs of ZNPs, including core, surface, and hybrid modifications clarifying the aim of the modification and its influence on phytochemicals-loaded ZNPs. Moreover, the variable used computational tools, including DoE, to optimize ZNPs and the emerging increasingly utilized exploitation of molecular dynamics (MD) and molecular docking to study the interaction between zein and other chemical entities are discussed.