Paclitaxel (PTX) is clinically recommended for the treatment of breast, ovarian and non-small cell lung cancer. This study delves into the impact of sugars (mannose or glucose) and sugar alcohols (mannitol or sorbitol) with varying spatial structures on the interfacial and thermodynamic behavior of the PTX/HS15/Tween80 micellar system. The research reveals that the presence of OH groups in sugars and sugar alcohols enhances hydrogen bonding force between surfactant and water, altering the critical micelle concentration (CMC) in solution and the surfactant’s arrangement at the interface, thus facilitating micelle formation and enhancing system stability. Dynamic light scattering (DLS) results show that the particle size of the PTX/HS15/Tween80 system is 11.69 nm, with micellar size showing a positive correlation with additive concentration. Sugar alcohols exhibit a more pronounced effect on increasing micelle size compared to sugars. Molecules featuring outward-facing OH groups demonstrating a greater ability to facilitate the formation of smaller micelle than those with inward-facing groups, emphasizing the influence of spatial structural differences. Stability experiments demonstrate that light transmission remains above 97 % in the system for 8 h after the addition of sugar, and the relative absorbance of PTX is maintained above 97 % within 6 h. Results from FD-B21 fluorescence probe release further confirm the positive impact of sugars and sugar alcohols on the stability of PTX/HS15/Tween80 micelles, highlighting stability differences based on molecules with distinct spatial structures. When OH groups on sugar or sugar alcohol molecules are more oriented in the same direction, intramolecular hydrogen bonds are formed, reducing spatial resistance and promoting the formation of micellar with smaller particle sizes. This process enhances physical stability by reducing inter-molecular collisions. In summary, the presence of sugars and sugar alcohols promotes micelle formation and boosts system stability, offering valuable insights for enhancing the stability of drug-loaded micelles.
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