Journal Article

Zein/Phospholipid Composite Nanoparticles for Successful Delivery of Gallic Acid into aHSCs: Influence of Size, Surface Charge, and Vitamin A Coupling

El-Maadawy, Walaa H, Yousry, Carol, ElMeshad, Aliaa Nabil, Shoukri, Raguia Aly, Radwan, Shaimaa Ali Ali

2020

Overview

Zein/phospholipid composite nanoparticles (CNPs) were developed as a delivery platform for gallic acid (GA), a polyphenolic compound with reported preclinical antifibrotic activities. However, the therapeutic applicability of GA is hampered owing to its low bioavailability and rapid clearance. Accordingly, we developed GA-loaded CNPs. The effect of their size, surface charge and targeting strategies was investigated and optimized, with the aim of enhancing their ability to deliver GA to the activated hepatic stellate cells (aHSCs) in order to suppress hepatic fibrosis progression. Different CNP systems were prepared and characterized with regard to their particle size, zeta potential, and GA entrapment efficiency (EE%). Also, they were statistically optimized via response surface methodology. The optimized systems were investigated with regard to their in vitro GA release, in vitro efficacy on aHSCs, and in vivo biodistribution in healthy rats. The GA-loaded cationic CNPs coupled with vitamin A (GA-CACNP/VA; 192 nm) showed high GA EE% (60% w/w), highest cellular internalization via active targeting, and more selective hepatic distribution, relative to free GA solution, GA-loaded anionic, and GA-loaded cationic systems. Furthermore, GA-CACNP/VA markedly triggered the apoptosis of aHSCs, repressed collagen deposition, and inhibited HSCs' activation to a lesser extent. The GA-CACNP/VA was shown to be a promising candidate for specific and controlled delivery of GA to aHSCs, which may provide an effective antifibrotic therapeutic approach.

• Publisher: Dove Medical Press Limited,Dove,Dove Medical Press
• Subject: Animals / Apoptosis - drug effects / Biological Availability / Collagen / Drug Carriers - chemistry / gallic acid / Gallic Acid - chemistry / Gallic Acid - metabolism / Gallic Acid - pharmacokinetics / Gallic Acid - pharmacology / Health aspects / hepatic fibrosis / hepatic stellate cells / Hepatic Stellate Cells - cytology / Hepatic Stellate Cells - drug effects / Hepatic Stellate Cells - metabolism / Lipids / Male / Nanoparticles / Nanoparticles - chemistry / Original Research / Particle Size / Phenols (Class of compounds) / phospholipids / Phospholipids - chemistry / Rats / Surface active agents / Surface Properties / Tissue Distribution / Vitamin A / Vitamin A - chemistry / zein / Zein - chemistry