Sirolimus encapsulation in Pluronic P123 and F108 self-assembled micelles for drug-coated balloons: Fabrication, characterization, and in vitro/ex vivo studies.

Drug-coated balloons (DCBs) are widely used in endovascular interventions to enable localized delivery of antiproliferative drugs during brief balloon inflation. This study compared Pluronic copolymer coatings (P123 and F108) loaded with sirolimus (SIR) on a PEBAX substrate, focusing on coating morphology, solid-state drug dispersion, hydrated dispersion state, and short-term release behavior relevant to DCB use. Pure P123 formed non-uniform coatings that became more continuous with increasing SIR content. Pure F108 formed uniform but fragile coatings that became more continuous at higher SIR fractions. FTIR and DSC analyses supported a dispersed drug state within the polymer matrices under the tested conditions. After hydration, nanoscale assemblies were observed by DLS and TEM, with size distributions influenced by temperature and formulation ratio. In vitro release over a procedure-relevant timeframe showed minimal early loss for P123 (approximately 1% during the initial interval), whereas F108 exhibited faster early release under the same conditions, indicating a higher propensity for premature drug loss. In vitro assays in vascular smooth muscle cells (VSMCs) showed that P123 and F108 alone had minimal impact on viability, while SIR-loaded coatings reduced VSMC proliferation and migration without evidence of overt cytotoxicity by Live/Dead staining. Ex vivo transfer experiments using swine aorta showed that P123 90:10 achieved the highest arterial transfer (86.52%), while higher SIR fractions reduced transfer efficiency; F108 formulations exhibited lower transfer than P123 under the same conditions. Overall, these results provide a DCB-oriented comparative dataset supporting P123-based formulations, particularly 90:10, as candidates for further study.