Schisandra lignans-loaded enteric nanoparticles: preparation, characterization, and in vitro–in vivo evaluation

Abstract

Schisandrae lignans (SL) have been well proven to possess hepatoprotective effect against the hepatic dysfunction induced by various chemical hepatotoxins. Deoxyschisandrin (DA) and schisantherin A (SA) are both considered as the major active components in SL. The objective of the study was to prepare and evaluate Schisandra lignans (composed of DA and SA)-loaded enteric nanoparticles produced by a novel toxic solvent-free modified spontaneous emulsification solvent diffusion (SESD) method. An organic Schisandra lignans/Eudragit^® S100 solution was injected into an aqueous poloxamer 188 solution under a agitation. The nanoparticles were characterized with respect to particle size distribution, morphology, encapsulation efficiency (EE) and physical stability of the drug, wettability, in vitro release and in vivo bioavailability. Nanoparticles with a smooth surface and dense structure were obtained with high EE (EE_DA >90%; EE_SA >85%). The drug was in a noncrystalline state in the matrix and physically stable for 120 days at room temperature. In vitro drug release study, the drug dissolution rate from the nanoparticles was significantly enhanced compared to the physical mixture and to the pure drug; the release profile of the nanoparticles was stable after 120 days. The appropriate size of nanoparticles (~93 nm), the solubilization of the surfactant, the noncrystalline state of the drug in the matrix and the fast dissolution rate contributed to a significantly enhanced oral bioavailability from the nanoparticles when compared to pure drug suspension.

Keywords::

• Fructus Schisandrae
• enteric polymer
• nanoparticles
• the modified spontaneous emulsification solvent diffusion method

Acknowledgments

The authors would like to acknowledge the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (No. 20101561), and the Natural Science Found of Beijing city of China (No. 7122176).

Declaration of interest

This study was supported by the Beijing Natural Science Foundation of China (7122176) and Military Medical Technology “Twelfth Five-Year” scientific research (CWS11J165).