Chitosan-decorated silibinin-hyaluronic acid conjugate for enhancing intestinal absorption and improving liver fibrosis.

Oral nanoparticles coated with chitosan (CS) exhibited improvement of gastrointestinal therapeutics delivery and enhancement of liver fibrosis therapy. Here, chitosan-modified silibinin-hyaluronic acid nanoparticles (CS/HA-SLB NPs) was fabricated. The silibinin (SLB) was linked with hyaluronic acid (HA) by ester bond to from HA-SLB conjugates, and then self-assembled by dialysis to form silibinin-hyaluronic acid nanoparticles (HA-SLB NPs), finally coated with CS through electrostatic attraction. The prepared CS/HA-SLB NPs had a particle size about 220 nm, approximate spherical profile, positive potential and drug loading 3.71 % or so. The in vitro release of CS/HA-SLB NPs showed sustained release feature, and the NPs were stable in simulated gastric fluid with minimal release. The results of in vivo pharmacokinetic experiments showed CS/HA-SLB NPs had longer tl/2 and larger AUC than that of others group (Free SLB, HA-SLB NPs). Moreover, the intestinal loop absorption and in vivo drug distribution study exhibited that CS/HA-SLB NPs had better enhancement intestine absorption and liver targeting ability. In CCl4-induced liver fibrosis mice, CS/HA-SLB NPs group had a better anti-liver fibrosis effect than that of others group. Taken together, these findings suggested that CS-decorated silibinin prodrug self-assembled nanoparticles were expected to improve the bioavailability and anti-hepatic fibrosis effect of SLB.