Cyclodextrin encapsulation of daidzein and genistein by grinding: implication on the glycosaminoglycan accumulation in mucopolysaccharidosis type II and III fibroblasts

Abstract

This work aimed to investigate the potential effect of cyclodextrin encapsulation on intrinsic ability of daidzein (DAD) and genistein (GEN) to inhibit the glycosaminoglycan (GAG) synthesis in fibroblasts originating from patients with mucopolysaccharidosis (MPS), type II and III. DAD or GEN encapsulation with either 2-hydroxypropyl-β-cyclodextrin or sulphobuthylether-β-cyclodextrin were achieved by neat grinding and were characterised by thermal analysis, X-ray powder diffraction, scanning electron microscopy and solubility testing which confirmed the complexes formation with increased solubility with respect to starting compounds. Both isoflavones, as well as their co-ground cyclodextrin complexes reduced GAG levels in the fibroblasts of MPS II and MPS III patients from 54.8–77.5%, in a dose dependent manner, without any significant cytotoxic effect. Cyclodextrin encapsulation did not change the intrinsically high effect of both DAD and GEN on the GAG level reduction in the treated cells, thus could be considered as a part of combination therapies of MPS.

Keywords:

• Daidzein
• genistein
• cyclodextrin
• neat grinding
• glycosaminoglycans

Acknowledgements

Authors are thankful to the Austrian Center for Electron Microscopy and Nanoanalysis Graz, Austria and Sanja Šimić for their help in conducting the SEM experiments. We thank to Vinko Nemec for assistance with TG analysis.

Disclosure statement

The authors report no conflicts of interests.

Additional information

Funding

This research was funded by the University of Zagreb (grant BM1.10) and Croatian Science Foundation (Grant number HRZZ-IP-09-2014-7367).