Development and evaluation of puerarin-loaded controlled release nanostructured lipid carries by central composite design

Abstract

The present work was aimed at developing optimized puerarin-loaded nanostructured lipid carrier (PA-NLC) on base of phospholipid complex. The puerarin phospholipid complex (PA-PC) was prepared by a solvent evaporation method and the formulation was confirmed according to the encapsulation efficiency (EE%). The hepatoprotective effect of PA-NLC on BRL 3A cell stimulated by ethanol was carried out using MTT assay, and cell imaging was done using an inverted phase contrast tissue culture microscope. The NLCs were produced by nanoemulsion method using glyceryl monostearate (GMS), olive oil, and Poloxamer 188 as the solid, liquid lipids, and surfactant. A single factor analysis determined the optimal ratio of solid lipid to liquid lipid. A three-factor, five-level central composite design (CCD) was used to predict response variables and construct 3D-response contour plots. The independent variables, which were the concentrations of PA-PC, total lipid, and surfactant affected particle size, surface charge of the nanoparticles, and the EE. An optimized NLC composition consisted of 31.25% PA-PC, 46.87% GMS, 9.38% olive oil, and 18.75% Poloxamer 188. The NLC had an average particle size of 159 ± 1.1 nm, zeta potential of −28.3 mV, EE% of 92.16%, and drug loading (DL%) of 5.75%. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) studies showed that the formation of NLC was accompanied by changes in crystallinity and intermolecular interaction. The PA-NLC system showed an enhanced therapeutic effect on alcohol-induced cell injury of BRL-3A.

Keywords:

• Puerarin
• phospholipid complex
• nanostructured lipid carrier
• central composite design
• alcohol-induced hepatocyte injury
• BRL-3A cell

Acknowledgments

The authors thank Jinghan Li from the College of Pharmacy, University of Minnesota – Twin Cities for suggestion to write the manuscript.

Disclosure statement

This research work is original and all the authors report no conflicts of interest.

Additional information

Funding

We acknowledged Shenyang Pharmaceutical University Scientific Research Foundation [GGJJ2015102] and Liaoning Province Science and Technology Project [No. 20170540864] for providing financial assistance for the project.