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

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.

Self-assembly of thyminyl l-tryptophanamide (TrpT) building blocks for the potential development of drug delivery nanosystems

“…Therefore, no loss of the self-assembly structure morphology of the selected particles was detected during this monitoring period, consistent with good stability of the TrpT assemblies. Our findings suggest that curcumin-loaded TrpT complexes could have potential in anti-inflammatory and antitumor therapy in analogy to other similar systems [71].…”

“…To this end, we sought to monitor the binding and release capabilities of TrpT nanostructures by loading them with curcumin, used to model a hydrophobic drug. Despite some potential therapeutic applications being somewhat compromised by its poor bioavailability, and rapid metabolism [69,70], curcumin has been shown to exhibit a range of anti-inflammatory, antibacterial, anticancer and anti-Alzheimer's properties [71].…”

Parenteral Lipid-Based Nanoparticles for CNS Disorders: Integrating Various Facets of Preclinical Evaluation towards More Effective Clinical Translation

“…For parenteral application, oil cores are usually composed of soybean oil, sunflower seed oil, olive oil, palm kernel oil esters, medium-chain triglycerides or fish oil [ 21 , 34 , 35 , 36 , 37 , 38 , 39 ]. It is advised to combine oils high in long-chain triglycerides, such as soybean or sunflower oil, which may improve drug penetration across the BBB due to linoleic acid content, with oils high in medium-chain triglycerides, having a higher solvent capacity and lower viscosity [ 39 , 40 ]. Because some of the free fatty acids from the selected oils, particularly oleic acid, can act as co-emulsifiers, the choice of the oil phase is critical not only for adequate drug loading but also for system stabilization [ 41 ].…”

“…Several techniques could be used to prepare lipid nanoparticles, including high-pressure homogenization (HPH) [ 25 , 34 , 36 , 38 , 40 , 44 ], thin film hydration followed by the sonication or filtration of liposomes [ 28 , 29 , 30 , 54 ], a combination of homogenization and sonication [ 46 , 47 ] or solvent-emulsification and evaporation techniques [ 45 ]. The physical and chemical complexity of the laboratory-scale prepared formulations is one of the facets that affect the scale-up of lipid nanoparticles, leading to difficulties in ensuring good stability during the shelf life [ 25 ].…”

Review of Curcumin and Its Different Formulations: Pharmacokinetics, Pharmacodynamics and Pharmacokinetic-Pharmacodynamic Interactions

“…Moreover, curcumin nanoparticles embedded in chitosan hydrochloride (CHC)-hyaluronic acid (HA)-PEG (CUR-PNPs) exhibited higher bioavailability than free curcumin, which was also effective in brain cancer therapy [74]. PEGylated form of curcumin nanoemulsion exhibited 2-3 fold improved bioavailability and plasma residence time within 20 min after intravenous infusion compared with non-PEGylated nanoemulsion or free curcumin solutions [75].…”