Superiority of DEAE-Dx-Stabilized Cationic Bile-Based Vesicles over Conventional Vesicles for Enhanced Hepatic Delivery of Daclatasvir

Abstract

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.

In Silico and In Vitro Studies for Benzimidazole Anthelmintics Repurposing as VEGFR-2 Antagonists: Novel Mebendazole-Loaded Mixed Micelles with Enhanced Dissolution and Anticancer Activity

“…Low PDI indicates that the BBV dispersion is homogeneous in nature. 60 The PDI was 0.17 ± 0.014, indicating good size homogeneity of the micellar solution.…”

“…The polydispersity index (PDI) is a measure of the distribution homogeneity of molecular size in a given sample. Low PDI indicates that the BBV dispersion is homogeneous in nature . The PDI was 0.17 ± 0.014, indicating good size homogeneity of the micellar solution.…”

Tailoring of Selenium-Plated Novasomes for Fine-Tuning Pharmacokinetic and Tumor Uptake of Quercetin: In Vitro Optimization and In Vivo Radiobiodistribution Assessment in Ehrlich Tumor-Bearing Mice

“…Dual solvent systems were employed as mobile phases for assessment of the RLY. Acetone was utilized as a mobile phase for estimation of free 99m TcO 4 − percentage, whereas the 99m Tc-colloidal impurities were appraised through using 0.5 M NaOH [33].…”

“…A standardized dose comprising similar injected quantity was concurrently counted and deemed as 100% activity. The uptake was described as % injected dose/g tissue (%ID/g) [33]. Muscles, bone, and blood were presumed to be 40, 10, and 7% of the whole-body weight, respectively.…”

Nanoparticle-Mediated Dual Targeting: An Approach for Enhanced Baicalin Delivery to the Liver

“…Previously, it was shown that encapsulation of atorvastatin calcium (AC) in NPs ≥ 200 nm improved induced hyperlipidemia in rats with no adverse effects despite their lower bioavailability compared to Lipitor. These findings were attributed to increased liver uptake of larger AC-NPs resulting in apparent lower bioavailability in blood but better liver targeting unlike smaller particles AC-NPs < 100 nm which showed higher bioavailability due to preferential circulation in the plasma, mediocre liver targeting and increased toxicity ( [69][70][71].…”