Novel composed galactosylated nanodevices containing a ribavirin prodrug as hepatic cell-targeted carriers for HCV treatment.

In this paper, we describe the preparation of liver-targeted nanoparticles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors in the liver (i.e., ASGPR in hepatocytes). These particles were obtained starting from a galactosylated phospholipid-polyaminoacid conjugate. This latter was obtained by chemical reaction of alpha,beta-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide (PHEA-EDA) with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl) sodium salt (DPPE), and subsequent reaction with lactose, obtaining PHEA-EDA-DPPE-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, i.e., RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. RBV tripalmitate-loaded nanoparticles were obtained starting from PHEA-EDA-DPPE-GAL copolymer by using the dialysis method. These particles showed spherical shape and nanometric size. By in vitro experiments the absence of haemolytic activity of RBV tripalmitate-loaded PHEA-EDA-DPPE-GAL nanoparticles and their specificity toward HepG2 were demonstrated by using a competitive inhibition assay in the presence of free GAL and assessing nanoparticle uptake in the presence of free GAL and/or non-galactosylated nanoparticles. This finding raises hope in terms of future nanoparticle-based liver-targeted drug delivery strategy for the hepatitis C treatment.

Phospholipid-polyaspartamide micelles for pulmonary delivery of corticosteroids.

A novel drug delivery system for beclomethasone dipropionate (BDP) has been constructed through self-assembly of a pegylated phospholipid-polyaminoacid conjugate. This copolymer was obtained by chemical reaction of α,ß-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethyleneglycol)2000] (DSPE-PEG(2000)-NH(2)). Benefiting from the amphiphilic structure with the hydrophilic shell based on both PHEA and PEG and many hydrophobic stearoyl tails, PHEA-PEG(2000)-DSPE copolymer was able to self assemble into micelles in aqueous media above a concentration of 1.23 × 10(-7)M, determined by fluorescence studies. During the self-assembling process in aqueous solution, these structures were able to incorporate BDP, with a drug loading (DL) equal to 3.0 wt%. Once the empty and BDP-loaded micelles were prepared, a deep physicochemical characterization was carried out, including the evaluation of mean size, PDI, ζ potential, morphology and storage stability. Moreover, the excellent biocompatibility of both empty and drug-loaded systems was evaluated either on human bronchial epithelium (16HBE) or on red blood cells. The cellular uptake of BDP, free or blended into PHEA-PEG(2000)-DSPE micelles, was also evaluated, evidencing a high drug internalization when entrapped into these nanocarriers and demonstrating their potential for delivering hydrophobic drugs in the treatment of pulmonary diseases.