Safety assessment of a newly synthesized copolymer for micellar delivery of hydrophobic caffeic acid phenethyl ester

Abstract

Caffeic acid phenethyl ester (CAPE), a major pharmacologically active component of poplar type propolis, is known for its proapoptotic, anti-inflammatory, antioxidant, antiviral, and enzyme inhibiting activities. The aim of this study was to perform an in vitro and in vivo safety assessment of a micellar system based on a newly synthesized copolymer, consisting of polyglycidol and poly(allyl glycidyl ether) (C₁₂-PAGE-PG) as a drug delivery platform for CAPE. The in vitro studies on HepG2 and L929 cells by MTT and LDH assays after treatment with the empty and CAPE-loaded micelles showed no cytotoxic effects of the empty micelles and retained cytotoxic activity of CAPE loaded in the micelles. No hemolysis or stimulation of mouse lymphocytes or macrophages was observed in vitro. In vivo hematological, biochemical, and histological assays on rats, treated with the empty (2580 and 5160 µg/kg) or CAPE-loaded (375 and 750 µg CAPE/kg) micelles did not reveal pathological changes of any of the parameters assayed after 14-days’ treatment. In conclusion, initial toxicological data characterize C₁₂-PAGE-PG as a non-toxic and promising copolymer for development of micellar drug delivery systems, particularly for a hydrophobic active substance as CAPE.

Keywords:

• Honeybee propolis
• polyglycidol copolymer
• CAPE-loaded micelles
• biocompatibility
• toxicology

Acknowledgements

The authors are grateful to Professor V. Bankova (Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences) for providing CAPE.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Science Fund (Bulgaria) [Project no. DN09/1-2016].