Advancements in Nanomedicine Platforms and Solid-State Engineering for Enhancing the Solubility of Apigenin: A Narrative Review.

Apigenin (APG) is a natural flavonoid with significant pharmacological potential, including antioxidant, anti-inflammatory, and anticancer properties. However, its clinical translation is severely constrained by its classification as a Biopharmaceutics Classification System (BCS) Class II compound, characterized by high permeability but poor aqueous solubility. This narrative review provides a critical, comparative evaluation of recent formulation strategies aimed at enhancing APG solubility and bioavailability. Literature published between 2013 and 2025 was systematically analyzed across PubMed, Scopus, and ScienceDirect. We establish a comparative framework categorizing formulations into nanoparticle-based delivery systems (eg, nanocrystals, SNEDDS, ethosomes, phytosomes, liposomes, mesoporous silica, micelles, and nanosuspensions) and solid-state modifications (eg, cocrystals, solid dispersions, inclusion complexes, and amorphous forms). Specifically, these strategies are differentiated through thermodynamic and kinetic perspectives: solid-state modifications predominantly lower lattice energy to raise equilibrium thermodynamic solubility, whereas nano-formulations enhance kinetic dissolution rates through surface area enlargement and improved mucosal absorption. By bridging fundamental thermodynamic mechanisms with translational challenges, this review provides strategic insights for the rational design of clinically viable apigenin delivery systems.