The preparation and pharmacokinetic evaluation of the self-assembled nanoparticles of the dihydroartemisinin prodrug of the reduction-sensitive / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare the self-assembled nanoparticles of the reduction-response dihydroartemisinin prodrug and study its pharmacokinetics. METHODS: Dihydroartemisinin as raw material, lauryl as the carrier, a dihydroartemisinin prodrug was designed and synthesized with disulfide bond as a connected arm. Molecular self-assembled technique was adopted to prepare the self-assembled nanoparticles of the dihydroartemisinin prodrug (DSCNs). Transmission electron microscopy (TEM) observed the nanoparticles morphology. Melvin granularity instrument measured the particle size, size distribution and Zeta potential. The properties of the optimized prescription were investigated, and their pharmacokinetics were evaluated. RESULTS: DSCNs were spherical with uniform size, the coating rate, drug loadings, average particle size, PDI and Zeta potential were (96.75±0.03)%, (80.60±2.6)%, (128.5±3.0) nm, (0.151±0.044) and (-16.6±0.9)mV, respectively. Vitamin E-TPGS (TPGS) was selected as the stabilizer of DSCNs to prevent the accumulation of nanoparticles, and DSCNs remained stable after 12 weeks. In vitrostudy showed that the release of DHA in prodrug was increased with the increase of the concentration of glutathione (GSH). Pharmacokinetic studies showed that DSCNs could significantly increase the blood concentration of DHA. CONCLUSION: The optimized preparation has long-term stability, which could be the basis for the further application of self-assembled nanoparticles to the drug sustained release system.