Coenzyme Q10-Polyethylene Glycol Monostearate Nanoparticles: An Injectable Water-Soluble Formulation

Abstract

Therapeutic applications of coenzyme Q10 (CoQ10) are greatly limited by its lack of solubility in aqueous media. In this study, polyethylene glycol monostearate (stPEG) was used to construct micelles containing CoQ10 as a new formulation. The micellar formulations (stPEG/CoQ10) were prepared using five types of stPEG with 10, 25, 40, 55, and 140 PEG repeat units, respectively. The micellar preparation was simple, consisting of only stPEG and CoQ10. Next, we compared the physical properties and blood circulation of these micelles. The CoQ10 load of this formulation was approximately 15 w/w%. Based on the dynamic light scattering method, the average molecular size of the stPEG/CoQ10 micelles was approximately 15 to 60 nm. The zeta potentials of these micelles were approximately -10 to -25 mV. The micelles using stPEG25, 40, and 55 demonstrated high solubility in water. Furthermore, these micelles had in vitro antioxidant activity. On comparing the blood circulation of micelles using stPEG25, 40, 55, and 140, micelles using stPEG55 had a significantly higher circulation in blood. The stPEG55/CoQ10 micelle demonstrated a protective effect against acetaminophen-induced liver injury in mice. In conclusion, these data indicate that the intravenous administration of the stPEG/CoQ10 micellar aqueous formulation is of great value against oxidant stress.

Keywords: coenzyme Q10; micellar formulation; oxidative stress; polyethylene glycol monostearate; water-soluble.

Figure 1

Relative fluorescence intensities (A,C) and emission maximums (λmax) of PNA as functions (B,D) of the logarithmic mass (A,B) or molar (C,D) concentrations of stPEG10 (●), stPEG25 (▲), stPEG40 (■), stPEG55 (◆), and stPEG140 (×). The values are the means ± S.D. for groups, with the experiment performed in triplicate for each sample.

Figure 2

Three-dimensional chromatogram of the stPEG25/CoQ10 micelle (A), stPEG40/CoQ10 micelle (B), stPEG55/CoQ10 micelle (C), and stPEG140/CoQ10 micelle (D). High-performance size-exclusion chromatography was performed using an HPLC system equipped with a photodiode array detector. A 7.8 × 300 mm, TSKgel^® G4000PWXL column was used at 40 °C. The mobile phase was water, and the flow rate was 1.0 mL/min. AU, Absobance Unit.

Figure 3

Result of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Inhibition of DPPH radical by stPEG/CoQ10 micelles at 1 mg/mL (A) and 2 mg/mL (B) as CoQ10 equivalents. The values are the means ± S.D. for groups, with the experiment performed in triplicate for each sample; * p < 0.05.

Figure 4

The CoQ10 levels in the plasma 1 h after a single injection of stPEG/CoQ10 micelles with 4 mg/kg in CoQ10 equivalents in mice. The values are the means ± S.D. for groups of four mice; ** p < 0.01, *** p < 0.001.

Figure 5

The effect of stPEG55/CoQ10 micelle treatment on aspartate aminotransferase (AST) (A) and alanine aminotransferase (ALT) (B) levels. Mice were treated with stPEG55/CoQ10 micelle (5, 15 mg/kg CoQ10 equivalent) 12 h before the administration of acetaminophen (APAP) 400 mg/kg. Bar represents means ± S.E., n = 4–5 mice per group; * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 6

Survival of mice given a lethal dose of APAP; the relationship between stPEG55/CoQ10 micelle administration and effectiveness. Mice were treated with stPEG55/CoQ10 micelle (5, 15 mg/kg CoQ10 equivalent) 12 h before the administration of APAP 750 mg/kg. Six mice were included in each group.