Optimization of the preparation of chitosan nanoparticles loaded with bifendate using the Box–Behnken design

The aim of this research is to explore new techniques for preparing a cross-linked three-dimensional network nanogel structure (CS-NPS) loaded with bifendate (DDB). The ionic cross-linking method was used to prepare CS-NPS from tripolyphosphate (TPP) and chitosan (CS), and DDB was then encapsulated in the nanogel structure to obtain DDB-CS-NPS. The preparation conditions were optimized through single-variable experiments and the Box–Behnken response surface method to obtain DDB-CS-NPS with good system stability, moderate particle size, and good encapsulation efficiency. It was found that when the TPP concentration was 1.5 mg/ml, the feed ratio was 3.8:1, and the ultrasound treatment time was 10 min and 53 s, the encapsulation efficiency predicted by the Box–Behnken response surface method could reach 89.38 %. A verification test showed that the actual average encapsulation efficiency of the DDB-CS-NPS reached 88.64 %, and the deviation between the predicted and the actual values was −0.8220 %. The average particle size of the samples was 644.8 nm, the polydispersity index was 0.301, and the zeta potential was 6.68 ± 1.29 mV. The results indicate that the proposed preparation process is feasible, the response surface test model can accurately predict the preparation condition area of DDB-CS-NPS, the deviation between the predicted encapsulation efficiency and the actual value is small, and the encapsulation efficiency meets the expected requirements. The DDB-CS-NPS obtained has a moderate particle size, a uniform distribution, and a relatively low potential. However, it may be prone to aggregation or coagulation, and so should be stored in a refrigerated condition. • Optimization of the preparation of bifendate-loaded chitosan nanoparticles. • Optimal preparation conditions predicted using the Box–Behnken response surface method. • The encapsulation efficiency was accurately predicted by the response surface model. • Experimental results demonstrate that the encapsulation efficiency was improved. • It enhances the bioavailability of the drug and the treatment of liver diseases.