Single and mixed micelles based on Polygonatum sibiricum polysaccharide for docetaxel delivery

Based on Polygonatum sibiricum polysaccharide (PSP), we synthesized a reduction-sensitive micellar system named FA-PSP-ss-BF to address the delivery challenges associated with hydrophobic docetaxel (DTX). The micelle incorporates folic acid (FA) to confer tumor-targeting capability, while ibuprofen (BF) serves both as a hydrophobic segment and an adjuvant for anticancer therapy. This single-component micelle exhibited a small particle size along with high drug encapsulation efficiency (EE) and loading capacity (LC) for DTX. Furthermore, we explored the feasibility of fabricating mixed micelles by combining this system with D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) to enhance drug delivery performance. The resulting mixed micelles showed a particle size of 150 nm, with EE and LC reaching 86.6% and 14.5%, respectively. Compared with the single micelle formulation, the mixed micelles demonstrated higher LC and a more compact particle size. Importantly, both the FA-PSP-ss-BF single micelles and the FA-PSP-ss-BF/TPGS mixed micelles displayed favorable biocompatibility in hemolysis and cytotoxicity assays. Moreover, DTX-loaded versions of both micellar systems exerted stronger inhibitory effects on 4T1 and HeLa cells than free DTX, with the mixed micelles showing superior activity. In conclusion, both micellar carriers, particularly the mixed micelle system, hold considerable promise for the effective delivery of hydrophobic therapeutics.