Development of silymarin-loaded polymeric micelles based on amphiphilic chitosan derivatives

Abstract

Keywords: Silymarin; Polymeric micelles; Chitosan; Physical entrapment methods

Objectives: The aim of this study was to incorporate silymarin into polymeric micelles which are amphiphilic chitosan derivatives to increase solubility of silymarin and to evaluate the properties of the micelles.

Methods: Three types of amphiphilic chitosan derivatives; N-benzyl-N,O-succinyl chitosan (BSCS), N-octyl-N-O-succinyl chitosan (OSCS) and N-naphthyl-N,O-succinyl chitosan (NSCS) were synthesized by reductive N-arylation and N,O-succinylation. Silymarin was incorporated into the micelles using various methods, including the dialysis method, the evaporation method, the dropping method and the O/W emulsion method. The entrapment efficiency, loading capacity, particle size and zeta potential were determined.

Results: Amphiphilic chitosan derivatives (BSCS, OSCS, NSCS) was synthesized and silymarin was incorporated into the inner core of polymeric micelles. The micelles prepared via the O/W emulsion method offered the highest percentage entrapment efficiency and loading capacity. The hydrophobic segment (benzyl, octyl and naphthyl) of polymers did not effect on the entrapment efficiency and loading capacity. We observed that increasing the initial amount of silymarin from 20% to 40% resulted in an increase in loading capacity from 194.1 to 334.7 μg/mg. This high amount reveals the successful encapsulation of the poor water soluble drugs into polymeric self-assemblies. The different methods also influenced the particle size of the micelles. The micelles ranged in size from 102 to 357 nm with negatively charge.

Conclusion: These amphiphilic chitosans was successfully synthesized and formed micelles in an aqueous solution by various methods. These micelles can be loaded with silymarin and demonstrate potential for increasing silymarin solubility. The micelles prepared from the O/W emulsion method demonstrated the highest entrapment efficiency and loading capacity.  Therefore, these micelles have promising potential as silymarin delivery systems.