Curcumin Loaded PEGylated Nanoemulsions Designed for Maintained Antioxidant Effects and Improved Bioavailability: A Pilot Study on Rats.

Jelena B Đoković,Bojan Batinić,Sanela M Savić,Jovana Aranđelović,Dragana Božić,Bojan D Marković,Danijela V Randjelović,Vladimir Stevanović,Jelena Antic-Stankovic,Miroslav M Savić,Nebojša D Cekić,Snežana D Savić,Ines Nikolic,Jelena R Mitrović

doi:10.3390/ijms22157991

Jelena B Đoković, Bojan Batinić + Show 12 more

Open Access

https://doi.org/10.3390/ijms22157991

Copy DOI

Abstract

The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of −40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078–0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings.

Highlights

Curcumin is a dietary polyphenolic compound derived from turmeric
This study shows that, while the nanoemulsion itself, as well as its PEGylated forms prolong circulation time of curcumin, it is almost completely eliminated from all the investigated matrices
Experimental design strategy was successfully applied to obtain the best template for long-term stable curcumin-loaded nanoemulsion formulations, intended for parenteral use

Summary

Introduction

Curcumin is a dietary polyphenolic compound derived from turmeric Zingiberaceae) with a long history of use as a traditional remedy in Chinese and Ayurvedic medicine [1,2]. It has been the subject of scientific interest for over 50 years [3], given its anti-inflammatory, antioxidant, anticancerous, antiepileptic, antidepressant, immunomodulatory, neuroprotective, antiapoptotic, and antiproliferative effects [4]. Its therapeutic potential has been explored in the treatment of various conditions such as pulmonary problems, cancer, sepsis and Alzheimer’s disease [5,6,7,8]. Wider therapeutic application of curcumin has been hindered by some of its physicochemical characteristics, such as poor aqueous solubility, degradation under alkaline conditions, heat and light sensitivity. The aim of our research was development of curcumin delivery system suitable for parenteral administration

Objectives

Methods

Results

Conclusion