The purpose of our
study was to improve the delivery of a direct-acting
antiviral drug, daclatasvir, to the site of action, liver tissues,
using physically and biologically stable cationic bile-based vesicles.
Accordingly, cationic bile-based vesicles were prepared as pro-bile-based
vesicles and diethylaminoethyl dextran (DEAE-Dx)-stabilized bile-based
vesicles to increase their stability without negatively affecting
their hepatic affinity. The prepared bile-based vesicles were characterized
for particle size, polydispersity index, ζ-potential, in vitro
daclatasvir release, and ex vivo permeation using non-everted gut
sac intestine. The in vivo biodistribution was experimented after
oral administration utilizing the radiolabeling assay, where the liver
showed the highest accumulation of the DEAE-Dx-stabilized bile-based
vesicles after 4 h, reaching a value of 4.6% ID/g of the total oral
administered dose of the labeled drug compared to drug solution, pro-bile-based
vesicles, and cationic bile-based vesicles where the accumulation
was 0.19, 1.3, and 0.31% ID/g, respectively. DEAE-Dx-stabilized bile-based
vesicles increased the drug deposition into the liver about 42-fold
compared to oral solution. The high physical stability and the high
resistance to opsonization and clearance show that DEAE-Dx-stabilized
bile-based vesicles could be efficiently applied for enhancing daclatasvir
delivery to the liver after oral administration.