Phenylephrine encapsulation in amphiphilic block copolymer micelles: drug–polymer interactions, solubilization and sustained release

In this work, we investigated the ability of various poloxamines (Tetronics) to solubilize phenylephrine and to achieve its controlled release through micellar encapsulation. Tetronics with varying hydrophilic–lipophilic balance (T304 T904, T908, T1107, T1304, and T1307) were selected to investigate the impact of polymer composition on drug–polymer interactions, micellar formation, Physicochemical properties and invitro behaviours such as release and anti-microbial activity. Cloud point and viscosity studies suggest that phenylephrine acts as a hydrophobic additive, inducing partial micellar growth, which correlates with a lower cloud point temperature and spherical copolymer architecture. Dynamic light scattering and transmission electron microscopy reveal the formation of stable, nanosized micelles, while drug loading increases micellar size, indicating drug encapsulation, which was further validated by a quantitative drug release study. In vitro release studies performed under physiological conditions (pH = 7.4, temperature = 37 °C) demonstrate that free phenylephrine is rapidly released, whereas encapsulation within Tetronic micelles extends the release duration to up to 72 h. Higuchi’s model was identified as the most suitable mathematical representation, consistent with a diffusion-controlled mechanism. Also, the phenylephrine-loaded formulations were evaluated against selected bacterial and fungal strains to obtain preliminary information on their biological behaviour. Since phenylephrine itself possesses little or no intrinsic antibacterial activity, the observed inhibitory effects should be considered properties of the overall micellar formulations rather than phenylephrine alone. Overall, the results demonstrate that Tetronic micelles are promising nanocarriers for improving phenylephrine solubilization and achieving sustained drug release.