Albumin self-modified liposomes for hepatic fibrosis therapy via SPARC-dependent pathways.

Abstract

Activated hepatic stellate cells (HSCs) have a central role in the progression of liver fibrosis and express a large amount of secreted protein, acidic and rich in cysteine (SPARC), a specific protein-binding protein. In this study, we reported the preparation and evaluation of naringenin (Nar) -loaded albumin self-modified liposomes (NaAlLs), which delivered Nar, a specific Smad3 inhibitor that blocked the TGF-β/Smad3 signaling pathway and played an anti-fibrosis role. After a series of characterization, it was found that NaAlLs had favorable dispersion (PDI<0.15) with an average particle size of about 120nm and high entrapment efficiency (>85%), albumin coated the surface of liposomes or embedded in phospholipid bilayer by interaction with the encapsulated naringenin and phospholipid molecules during the preparation of liposomes. The amount of albumin modified to the surface of NaAlLs by this method is not only more than that of the physical adsorption method, but also the binding force between albumin and liposomes is stronger. The albumin modified to the surface of NaAlLs greatly reduced the aggregation of liposomes and drug leakage and increased the stability of liposomes. More importantly, the uptake of NaAlLs by activated HSCs was 1.5 times higher than that of Nar-loaded liposomes (NaLs), suggesting that NaAlLs specifically increased targeting of activated HSCs via albumin and SPARC-dependent pathways. As expected, NaAlLs was more effective in improving liver fibrosis than the NaLs or the inclusion complex solution of Nar and Hydroxypropyl-β-cyclodextrin (NaICS). The results suggested that NaAlLs was a promising drug delivery system, which could target drug delivery to activated HSC for the treatment of liver fibrosis.