Abstract:

pH-sensitive micelles BUDA-pentanolamine-(mPEG-NH₂) (BPAU) were synthesized with traditional pH-sensitive micelle materials 5-amino-1-pentanol (pentanolamine), 1, 4-butanediol diacrylate (BUDA) and amino group functionalization methoxypolyethylene glycol (mPEG-NH₂) as raw materials by self-assembly. Then, with trieneurushiol phenol borate derivative (URU-NH₂) as the hydrophobic unit and galactose (Gal) as the recognition unit, the pH-sensitive BPAU-NH₂-Gal nanomicelle was synthesized. And then, Paclitaxel (PTX) was used as the test drug, and nano-drug loaded micelles (PTX@BPAU-NH₂-Gal) were prepared by dialysis. By nuclear magnetic (NMR), gel chromatography (GPC), surface/interfacial tension, Zeta potential analysis, micelle structure, average relative molecular mass (M_w) and critical micelle concentration (CMC), Zeta potential were characterized. The morphology of drug-loaded micelles was characterized by TEM, and the particle size was determined by DLS.High-performance liquid chromatography (HPLC) was used to determine the encapsulation efficiency and drug loading quantity of PTX. Dynamic membrane dialysis was used to investigate the release and uptake characteristics of drug-loaded micelles at different pH values in vitro. The results showed that BPAU-NH₂-Gal was synthesized successfully, and the M_w value of micelle BPAU-NH2-Gal was about 15 550, dispersion index (PDI) was 1.49, the CMC value was about 90.29 mg/L, and the Zeta potential value was 29.69 mV. The drug-loaded micelle PTX@BPAU-NH₂-Gal had an irregular elliptical structure with the average particle size about 195 nm; the encapsulation rate of paclitaxel was 92.51%, the drug load quantity was 31.76%.When the pH value was 4.5, the release rate was significantly higher than that in the environment with pH value of 6.8 and 7.4, and the micelle release had obvious pH responsiveness property.When the pH value of the buffer solution was 4.5, 6.8, and 7.4, the cumulative release rate of paclitaxel from the drug-loaded micelle within 90 h were 50.00%, 34.26% and 9.00%, respectively, which showed low toxicity to LO2 and high activity against HepG2.

Key words: urushiol, drug-loaded micelles, paclitaxel, pH-responsive, HepG2