Biodegradable and biocompatible spherical dendrimer nanoparticles with a gallic acid shell and a double-acting strong antioxidant activity as potential device to fight diseases from «oxidative stress»

Gallic acid (GA) is a natural polyphenol with remarkable antioxidant power present in several vegetables and fruits. A normal feeding regime leads to a daily intake of GA which is reasonably regarded as ‘‘natural’’ and ‘‘safe’’ for humans. It owns strong potentials as alternative to traditional drugs to treat several diseases triggered by oxidative stress (OS), but poor gastrointestinal absorbability, pharmacokinetic drawbacks and fast metabolism limit its clinical application. In this work, a fifth generation polyester-based dendrimer was firstly prepared as a better absorbable carrier to protect and deliver GA. Then, by its peripheral esterification with GA units, a GA-enriched delivering system (GAD) with remarkable antioxidant power and high potential against diseases from OS, was achieved. Scanning Electron Microscopy results and Dynamic Light Scattering analysis, revealed particles with an average size around 387 and 375 nm respectively and an extraordinarily spherical morphology. These properties, by determining a large particles surface area, typically favor higher systemic residence time and bio-efficiency. Z-potential of -25 mV suggests satisfactory stability in solution with tendency to form megamers and low PDI. GAD showed intrinsic antioxidant power, higher than GA by 4 times and like prodrugs, it can carry contemporary several bioactive GA units versus cells. In physiological condition, the action of Pig Liver Esterase (PLE), selected as a model of cells esterase, hydrolyzes GAD to non-cytotoxic small molecules, thus setting free the bioactive GA units, for further antioxidant effects. Cytotoxicity studies performed on two cell lines demonstrated a high cell viability.