Abstract: With the development of nano-medicine, a novel kind of self-assembled nanoparticle was fabricated through electrostatic crosslink method using negative-charged lecithin and positive-charged chitosan. This kind of self-assembled nano-carrier could be used to improve oral bioavailability of drugs with poor solubility. In this study, we utilized this nano-carrier to facilitate the drug delivery of berberine hydrochloride, whose water solubility is low to 1:200（g:mL）. At the same time, the method for entrapment efficiency（EE）measurement was established. Afterwards, orthogonal screening was used to determine the optimal formulation of drug-loaded self-assembled nanoparticle, in which entrapment efficiency（EE）was set as evaluation indicator. In the selected formulation, pH value of water phase was 8.0, volume ratio of ethanol phase/water phase was 8:92, and mass ratio of lecithin/chitosan was 20:1. Three batches self-assembled nanoparticle were prepared under the selected formulation, and evaluation results showed that the average particle size, Zeta potential and entrapment efficiency was（214.8±9.3）nm,（24.3±3.1）mV and（82.4±5.2）%, separately. Berberine hydrochloride loaded self-assembled nanoparticle remains high stability under 4 ℃ storage, which provided the basis for practical application.

Key words: self-assembled nanoparticle, berberine hydrochloride, drug delivery, orthogonal screening, formulation selection