The effect of surface treatment on the brain delivery of curcumin nanosuspension: in vitro and in vivo studies

Abstract

Background: Curcumin, a bioactive component with multiple characteristics, has been shown to have many therapeutic effects. However, there are several limitations regarding the use of curcumin such as instability, low solubility, poor bioavailability, and rapid elimination. Different approaches have been used to solve these problems. Materials and methods: In this study, surface-modified nanosuspension (NS) is investigated as a novel brain delivery system. Two different methods were used for the preparation of nanosuspensions with two different stabilizers. The surface of the nanosuspensions was coated with D-α-tocopheryl polyethylene glycol 1,000 succinate (TPGS) and Tween 80 using physical adsorption. Curcumin NSs were prepared using two different top-down techniques by high-pressure homogenizer and probe sonicator. A validated sensitive and selective high-performance liquid chromatography method using fluorescence detection was used for the determination and quantification of curcumin. Pharmacokinetics and biodistribution of curcumin NSs and solutions after intravenous administration in rats were studied. Results: Higher levels of curcumin in the brain were detected when Tween 80-coated NS was used compared with the curcumin solution and TPGS coated NS (TPGS-NS) (P-value<0.05). Absorption of ApoE and/or B by Tween 80-coated nanoparticles (NPs) from the blood were caused transferring of these NPs into the brain using receptor-mediated endocytosis. Distribution of TPGS-NS in the brain compared with the curcumin solution was higher (P-value<0.05). Higher levels of curcumin concentration in the liver, spleen, and lung were also observed with TPGS-NS. Conclusion: The results of this study indicate that the surface-coating of NSs by Tween 80 may be used to improve the biodistribution of curcumin in the brain.

Keywords: TPGS; Tween 80; biodistribution; curcumin; nanosuspensions; pharmacokinetics.

Figure 3

X-ray powder diffractometry (A) of curcumin, (B) physical mixture of TPGS solution and curcumin, (C) physical mixture of Tween solution and curcumin, (D) NS without surfactant, (E) Tween-NS, and (F) TPGS-NS. Abbreviations: TPGS, D-α-tocopheryl polyethylene glycol 1,000 succinate; NS, nanosuspension.

Figure 1

Size distribution by intensity for TPGS-NS and Tween-NS. Abbreviations: TPGS, D-α-tocopheryl polyethylene glycol 1,000 succinate; NS, nanosuspension.

Figure 2

SEM photographs of curcumin nanosuspensions: TPGS-NS (A–C) and Tween-NS (D–F). Abbreviations: TPGS, D-α-tocopheryl polyethylene glycol 1,000 succinate; NS, nanosuspension; TPGS-NS, curcumin and TPGS; Tween-NS, curcumin and Tween 80.

Figure 4

Dissolution curve of the TPGS-NS, Tween-NS and pure curcumin. All values reported are means±SE (n=3). Abbreviations: TPGS, D-α-tocopheryl polyethylene glycol 1,000 succinate; NS, nanosuspension; TPGS-NS, curcumin and TPGS; Tween-NS, curcumin and Tween 80.

Figure 5

Plasma concentration of solution and NSs in rat. All values reported are means±SE (n=6). (TPGS-NS,Tween-NS, solution). Abbreviations: TPGS, D-α-tocopheryl polyethylene glycol 1,000 succinate; NS, nanosuspension; TPGS-NS, curcumin and TPGS; Tween-NS, curcumin and Tween 80; Solution, DMA, PEG 400, and isotonic dextrose solution.

Figure 6

The tissue curcumin concentrations versus time after intravenous administration of solution and NSs. All values reported are means±SE (n=6). Abbreviations: TPGS, D-α-tocopheryl polyethylene glycol 1,000 succinate; NS, nanosuspension; TPGS-NS, curcumin and TPGS; Tween-NS, curcumin and Tween 80; Solution, DMA, PEG 400, and isotonic dextrose solution.

Figure 7

Brain curcumin concentrations versus time after intravenous administration of solution and NSs. All values reported are means±SE (n=6). Abbreviations: TPGS, D-α-tocopheryl polyethylene glycol 1,000 succinate; NS, nanosuspension; TPGS-NS, curcumin and TPGS; Tween-NS, curcumin and Tween 80; Solution, DMA, PEG 400, and isotonic dextrose solution.