A Comprehensive Review of Casein Nanomaterial in Drug Delivery
Casein, a common milk phosphoprotein, has been increasingly investigated as a potential biopolymer for drug delivery due to its amphiphilicity, biocompatibility, and capacity to selfassemble into micellar nanostructures. These features enable the encapsulation of both hydrophilic and hydrophobic drugs and have prompted increasing research interest in their application as a nanocarrier system. This review critically assesses the current state of research on casein-based nanomaterials, focusing on physicochemical features, formulation techniques, and application across oral, Ocular and parenteral drug delivery systems. Available studies suggest that casein-based nanoparticles may improve drug solubility, encapsulation efficiency, and controlled release. However, the majority of the evidence is derived from in vitro experiments and limited in vivo models, with relatively few studies addressing pharmacokinetic behaviour or clinical relevance. In addition, substantial variability in formulation methods, including differences in preparation techniques and particle characteristics, complicates reproducibility and cross-study comparison. Key challenges such as long-term stability, scalability, and potential immunogenicity remain insufficiently addressed. Furthermore, claims of enhanced targeting or therapeutic efficacy are often based on indirect or preliminary data rather than validated in vivo outcomes. Overall, while casein-based nanomaterials represent a promising platform for drug delivery, the current evidence remains fragmented and further standardised in vivo and clinically oriented investigations are required to establish their translational potential.