Development and Characterization of Curcumin-Silver Nanoparticles as a Promising Formulation to Test on Human Pterygium-Derived Keratinocytes.

Gianmarco Stati,Roberta Di Pietro,Stefanos Mourdikoudis,Francesco Rossi,Nguyễn Thi Kim Thanh,Le Duc Tung,Thithawat Trakoolwilaiwan

doi:10.3390/molecules27010282

Abstract

Pterygium is a progressive disease of the human eye arising from sub-conjunctival tissue and extending onto the cornea. Due to its invasive growth, pterygium can reach the pupil compromising visual function. Currently available medical treatments have limited success in suppressing efficiently the disease. Previous studies have demonstrated that curcumin, polyphenol isolated from the rhizome of Curcuma longa, induces apoptosis of human pterygium fibroblasts in a dose- and time-dependent manner showing promising activity in the treatment of this ophthalmic disease. However, this molecule is not very soluble in water in either neutral or acidic pH and is only slightly more soluble in alkaline conditions, while its dissolving in organic solvents drastically reduces its potential use for biomedical applications. A nanoformulation of curcumin stabilized silver nanoparticles (Cur-AgNPs) seems an effective strategy to increase the bioavailability of curcumin without inducing toxic effects. In fact, silver nitrates have been used safely for the treatment of many ophthalmic conditions and diseases for a long time and the concentration of AgNPs in this formulation is quite low. The synthesis of this new compound was achieved through a modified Bettini’s method adapted to improve the quality of the product intended for human use. Indeed, the pH of the reaction was changed to 9, the temperature of the reaction was increased from 90 °C to 100 °C and after the synthesis the Cur-AgNPs were dispersed in Borax buffer using a dialysis step to improve the biocompatibility of the formulation. This new compound will be able to deliver both components (curcumin and silver) at the same time to the affected tissue, representing an alternative and a more sophisticated strategy for the treatment of human pterygium. Further in vitro and in vivo assays will be required to validate this formulation.

Highlights

Pterygium, a wing-shaped fibro-vascular overgrowth arising from the white and clear part of the eye, is able to spread through the corneoscleral junction and to invade the cornea
We applied some changes to the green synthesis method to improve the quality of our nanocomposite intended for clinical use
The temperature of the reaction was increased from 90 ◦ C (Bettini’s method) to 100 ◦ C and the pH was carefully controlled to values slightly below 9 in the course of the reaction to achieve the highest possible reactivity of curcumin and silver, together with the lowest degree of alkaline

Summary

Introduction

A wing-shaped fibro-vascular overgrowth arising from the white and clear part of the eye (sclera), is able to spread through the corneoscleral junction and to invade the cornea. Different surgical procedures have been developed to treat this condition, but all available methods can lead to a relapse of the disease which always consists in a faster growing and more aggressive form of pterygium [1]. Several medical therapies, such as the administration of thiotepa, 5-fluoruracil, mitomycin C, VEGF inhibitors and beta irradiation, have been used. These treatments have not led to a consistent reduction in the relapse cases. Several research groups reported a different percentage of relapses, corneal scarring and side effects respectively, due to surgical procedure and drugs utilized [2,3,4]

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