Nanosuspensions as delivery system for gambogenic acid: characterization and in vitro/in vivo evaluation

Abstract

Nanosuspensions (NS) can enhance the saturation solubility and dissolution velocity of poorly soluble drugs. PEG as a non-ionic surfactant plays an important role in surface modification of nanoparticles for prolonging in vivo circulation. In this study, anti-solvent precipitation method was introduced to prepare gambogenic acid nanosuspensions (GNA-NS) with PVPK30 and PEG2000 as stabilizers to settle the disadvantages of GNA. The obtained nanoparticles were spherical with a mean particle size of 183.7 nm and a zeta potential of −22.8 mV. The entrapment efficiency and drug loading of the resultant formulation were 97.3 and 29.73%. X-ray diffraction analysis confirmed the amorphous phase of GNA in NS. Fourier transform infrared indicated there may be hydrogen bond interaction between the drug and excipients. After lyophilization of GNA-NS, the freeze-dried powder displayed sufficient long-term physical stability at 4 and 25 °C. In comparison to GNA solution, in vitro studies of GNA-NS showed much slower release and higher cytotoxicity in HepG2 cells. What’s more, the pharmacokinetic study in rats revealed that the AUC_0–∞ and t_1/2 of GNA-NS were increased 2.63- and 1.77-fold than that of the reference formulation. Taken together, in vitro/in vivo evaluations showed NS would be an effectively strategy to change the poor aqueous solubility and prolong the half-life for GNA. The GNA-NS with enhanced bioavailability and drug efficacy provided a promising delivery system for the application of GNA.

Keywords:

• Cytotoxicity
• gambogenic acid
• in vivo pharmacokinetics
• in vitro release
• nanosuspensions

Acknowledgement

The authors gratefully acknowledge Wang Xiaoshan’s laboratory for the gift samples.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

The authors also acknowledge the funding support from the National Natural Science Foundation of China (Grants 51303006) and the Provincial Natural Science Foundation (1408085MH196, KJ2012ZD09, 10040606Q36) of Anhui Province.

Supplementary material available online

Supplementary Figure S1 and Tables s1 and S2