Preparation and in-vitro/in-vivo evaluation of curcumin nanosuspension with solubility enhancement

J Pharm Pharmacol. 2016 Aug;68(8):980-8. doi: 10.1111/jphp.12575. Epub 2016 Jun 10.

Abstract

Objectives: We developed Cur nanosuspension (Cur-NS) with PVPK30 and SDS as stabilizers to improve poor water solubility and short biological half-time of Cur.

Methods: Physicochemical characterization of Cur-NS was characterized systematically. The in-vitro dissolution, cytotoxicity and in-vivo pharmacokinetic experiments of Cur-NS were also evaluated.

Key findings: Scanning electron microscope indicated that the morphologies of Cur-NS were spherical or ellipsoidal in shape. X-ray diffraction verified that Cur was successfully developed as nanoparticles with an amorphous phase in Cur-NS. Fourier transform infrared spectroscopy suggested there was no degradation about Cur in the Cur-NS. Furthermore, the in-vitro study showed that the cumulative release of the Cur-NS was 82.16 ± 2.62% within 34 h and the cytotoxicity of the Cur-NS against HepG2 cells was much better than raw Cur. Besides, in-vivo pharmacokinetics in rats by intravenous injection displayed that the in-vivo process of Cur-NS pertained to two-compartment model. Meanwhile, the t1/2 and AUC0-t of Cur-NS were enhanced by 11.0-fold and 4.2-fold comparing to Cur solution.

Conclusions: The Cur-NS significantly increased the water solubility and half-time of Cur, suggesting its potential as a nanocarrier in the delivery of Cur for future clinical application.

Keywords: curcumin; cytotoxicity; intravenous injection; nanosuspension; pharmacokinetics.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Area Under Curve
  • Biological Availability
  • Curcuma / chemistry
  • Curcumin / administration & dosage*
  • Curcumin / chemistry
  • Curcumin / pharmacokinetics
  • Curcumin / pharmacology
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / standards
  • Female
  • Hep G2 Cells
  • Hepatoblastoma* / drug therapy
  • Humans
  • Liver Neoplasms* / drug therapy
  • Male
  • Nanoparticles / chemistry*
  • Particle Size
  • Pharmaceutical Solutions / chemistry
  • Polyvinyls
  • Rats, Sprague-Dawley
  • Sodium Dodecyl Sulfate / analogs & derivatives
  • Solubility
  • Spectroscopy, Fourier Transform Infrared
  • Water
  • X-Ray Diffraction

Substances

  • Antineoplastic Agents, Phytogenic
  • Pharmaceutical Solutions
  • Polyvinyls
  • poly(vinyl phenyl ketone)
  • sodium dodecyl dioxyethylene sulfate
  • Water
  • Sodium Dodecyl Sulfate
  • Curcumin