Elucidating drug-carrier interactions and release from PCL and PLA microspheres prepared by PES membrane emulsification: a strategy integrating molecular docking.

PES membrane, with its excellent mechanical properties and biocompatibility, facilitate many pharmaceutical applications, particularly to replace SPG and PVDF membranes for membrane emulsification for microspheres preparation. Despite the extensive use of polycaprolactone (PCL) and polylactic acid (PLA) as drug carriers, their interactions with drug molecules have rarely been directly compared. This knowledge gap directly impacts the rational design and control of drug release rates from microspheres made of these polymers. Hence this study focuses on the use of novel PES membrane emulsification technology to investigate the preparation and properties of the PCL and PLA microspheres for sustained drug release. The effect of additives for casting solutions of membrane were investigated for comparing the size distribution of PCL and PLA microspheres. The encapsulation of three phenolic drug contents (i.e. baicalin, quercetin and bakuchiol) were conducted using PCL and PLA as the carrier of the microspheres. The drug release rate as well as other pharmaceutic characteristics were evaluated, while the molecular action between the drug carriers and drug contents were estimated using molecular docking. The experimental results confirmed that microspheres with small and uniform particle size, measured at 40.72 μm, could be achieved using casting solution of 18 wt% prepared PES membrane with additives. In contrast to the smooth surface of PCL microspheres, their PLA counterparts exhibited a distinctly porous morphology. Molecular docking simulations suggested baicalin exhibit strong binding affinity with PCL and PLA reaching -3.36 kcal/mol and -2.32 kcal/mol, together with its low solubility and molecular size, resulted in slowest release of 0.52% on 17th day when encapsulated in both PCL and PLA microsphere. Bakuchiol exhibited weaker binding affinity with PLA than with PCL, resulting in a higher release rate from PLA microspheres. Quercetin, conversely, showed weaker binding affinity with PCL than with PLA, resulting in a higher release rate from PCL microspheres. Among them, C-Bak microspheres showed the highest 48 h wound closure rate (46.09%), while A-Que microspheres exhibited the best cell viability (287.17%).