Niosomes as a versatile nanocarrier for antiviral agents: Enabling delivery of both hydrophilic and hydrophobic drugs.

The development of nanocarrier systems for antiviral delivery presents a promising approach to overcoming the physicochemical and therapeutic limitations of conventional drugs. In this study, we optimized a thin-film hydration method to produce stable niosomes, capable of encapsulating three antiviral agents: mycophenolic acid, ribavirin, and curcumin. Physicochemical characterization revealed niosome sizes (80-200 nm), monodisperse distribution (PdI < 0.3), and negative surface charge, indicating good colloidal stability and biocompatibility. Encapsulation efficiency ranged from 35 % to 78 %, depending on the physicochemical properties of each compound. Thermal analysis confirmed the thermodynamic stability of the formulations, with no degradation observed below 150 °C. Scanning electron microscopy revealed well-defined vesicular morphology and dynamic light scattering analysis of pellet fractions confirmed homogenous particle populations suitable for therapeutic application. Biological assays against herpes simplex virus type 1 and vesicular stomatitis virus showed that drug-loaded niosomes exerted potent antiviral effects at nanogram concentrations, with significantly reduced cytotoxicity. Selectivity index values increased by up to 108-fold compared to the non-encapsulated compounds, underscoring the therapeutic advantage of nanoencapsulation. Notably, encapsulated mycophenolic acid and the mycophenolic acid-curcumin combination exhibited enhanced efficacy against herpes simplex virus type 1, a virus known for its resistance to standard antiviral therapies. In summary, we developed stable and reproducible niosomal formulations capable of efficiently encapsulating mycophenolic acid, ribavirin, and curcumin, achieving high loading efficiency and strong antiviral activity against herpes simplex 1 and vesicular stomatitis virus with markedly reduced cytotoxicity. Combination analysis of mycophenolic acid and curcumin revealed synergistic effects on cell viability but antagonistic interactions in antiviral assays, highlighting the importance of assessing drug combinations across different biological contexts. These findings position niosomes as a promising platform for antiviral delivery and provide a solid basis for future optimization and translational studies.