Preparation and characteristics of novel Jerusalem artichoke polysaccharides-based polymeric micelles for poorly water-soluble drug delivery

To develop a novel Jerusalem artichoke polysaccharide (JAP)-based delivery system for poorly water-soluble drugs (PWSDs), JAP-SA polymer and florfenicol (FFC)/JAP-SA polymer micelles were prepared. The preparation process was optimized using response surface methodology, with encapsulation efficiency (EE) and drug loading capacity (DLC) as evaluation criteria. Under the optimized conditions [mass ratio of FFC to JAP-SA (1:1), stirring time (5.4 h), and stirring speed (700 r/min)], the EE and DLC reached 69.11 ± 2.04% and 11.99 ± 2.02%, respectively. SEM, TEM, and laser diffraction particle size analysis revealed that the drug-loaded micelles exhibited a unimodal size distribution with an average diameter of 198.33 ± 0.25 nm and a near-spherical morphology. The micelles demonstrated favorable stability, blood compatibility, and cytocompatibility, as assessed through stability testing (STS), erythrocyte hemolysis assay (EHT), and MTT assay. The critical micelle concentration (CMC) of the FFC/JAP-SA micelles, as determined by pyrene fluorescence spectroscopy (PFS), was 19.92 ± 2.01 µg/mL in water and 10.96 ± 1.18 µg/mL in phosphate-buffered saline (PBS). In vitro release studies showed that the FFC/JAP-SA micelles provided sustained drug release in both simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 6.8), with release kinetics indicating acid-responsive behavior. Additionally, antibacterial efficacy was observed to be concentration-dependent. Pharmacokinetic analysis yielded a time to peak concentration (T max ) of 1.00 ± 0.18 h, a mean residence time (MRT 0-t ) of 8.34 ± 0.68 h, and an elimination half-life (T 1/2β ) of 2.93 ± 2.72 h. These results demonstrate that the FFC/JAP-SA micelles significantly enhanced the aqueous solubility of encapsulated FFC compared to FFC powder, thereby establishing a promising foundation for improving therapeutic efficacy and reducing side effects associated with PWSDs.