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 À22.8 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 longterm 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 0-1 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. KeywordsCytotoxicity, gambogenic acid, in vivo pharmacokinetics, in vitro release, nanosuspensions History

Preparation, characterization and preliminary pharmacokinetic study of pH-sensitive Hydroxyapatite/Zein nano-drug delivery system for doxorubicin hydrochloride

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Preparation and preliminary pharmacokinetics study of GNA-loaded zein nanoparticles

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