Abstract
Chronic inflammation is considered as one of the challenging diseases, and overproduction of reactive oxygen species (ROS) is strongly related to the onset of chronic inflammation. Therefore, antioxidant and anti-inflammatory approaches are particularly becoming suitable treatment and prevention of inflammation. Curcumin (CUR), a main component of turmeric extract, is well known as an effective agent in both antioxidant and anti-inflammatory activities; however, there are still some limitations of its use including poor water solubility, low bioavailability, and oxidation by ROS. Nanotechnology has been used as a drug delivery system, which is a promising approach in overcoming the aforementioned drawbacks of CUR; hence, it improves the antioxidant and anti-inflammatory effects of conventional medications. In this research, silica-containing redox nanoparticles (siRNP) were designed with the size of several tens of nanometers, prepared by self-assembly of an amphiphilic block copolymer consisting of drug absorptive silica moiety and ROS-scavenging nitroxide radical moiety in the hydrophobic segment. CUR was simply encapsulated into siRNP through the dialysis method, creating CUR-loaded siRNP (CUR@siRNP), which significantly improved the water solubility of CUR. The efficient antioxidant activity and anti-inflammatory effect of CUR@siRNP in vitro were also improved via 2,2-diphenyl-1-picrylhydrazyl assay and lipopolysaccharide-induced macrophage cell line activation, respectively. Oral administration of CUR@siRNP showed improvement in pharmacokinetic profile in vivo including AUC and Cmax values as compared to free CUR. Furthermore, the anti-inflammatory effect of nanoformulation was investigated in the colitis mouse model induced by dextran sodium sulfate.
Highlights
According to the World Health Organization (WHO), chronic inflammation is considered one of the greatest threats to other chronic diseases
The results showed that CUR@silica-containing redox nanoparticles (siRNP) significantly improved the water solubility and bioavailability of CUR after oral administration
CUR is an antioxidant substance with extremely poor solubility in an aqueous solution (
Summary
According to the World Health Organization (WHO), chronic inflammation is considered one of the greatest threats to other chronic diseases. Chronic inflammation, is characterized for longterm persistence from months, years to even decades. Chronic inflammation is strongly related to many challenging diseases, such as cancer, heart disease, diabetes, and Alzheimer’s disease [2]. The discovery of reactive oxygen species (ROS) features its active roles in many pathways, including oxidative stress, which progressed chronic inflammation. It has been reported that oxidative stress or overproduced ROS accumulatively induces chronic inflammation as both signalling molecules and inflammatory mediators [3]. Due to a single electron on the outer shell, ROS are unstable and may react with adjacent molecules to maintain electrical homeostasis [4]. Endogenous ROS accumulation activates thioredoxin, which interacted protein (TXNIP) complex [4]. The complex detached, enabling TXNIP to bind with NLRP3 inflammasome.
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