In vitro evaluation of antioxidant activity and biocompatibility of caffeic acid phenethyl ester loaded in polymeric micelles

Background Caffeic acid phenethyl ester (CAPE) (a component of honey bee propolis) possesses various biological activities. However, the high lipophilicity of CAPE limits its applications, since it hinders both the formulation of stable drug dosage forms and its bioavailability. In attempt to overcome these problems, CAPE was loaded in micelles based on poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO-PCL-PEO) triblock copolymer and its derivatives, comprising cinnamyl-modified segments, structurally similar to the CAPE molecule. The similarity between CAPE and the micellar core resulted in a higher loading degree. Objective The present study evaluated the safety and antioxidant activity of the newly developed CAPE-loaded micelles in human endothelial Ea.hy926 cells in vitro. Result Both empty and CAPE-loaded micelles demonstrated a good hemocompatibility. A cell viability evaluation performed by MTT test and LDH leakage assay showed a good safety profile of empty micelles even in the highest concentrations (125 and 250 µg/ml). In contrast, free and micellar CAPE caused a statistically significant decrease in Ea.hy926 cell viability. DPPH and ABTS• + assay revealed that the radical scavenging activity of CAPE loaded into the micelles was preserved. In a model of H 2 O 2 -induced oxidative stress in Ea.hy 926 cells, both pure and micellar CAPE provided significant protection against H 2 O 2 -induced damage. However, even in low concentrations (0.1 µg/ml), CAPE loaded in the cinnamyl-modified micelles showed better antioxidant protection, compared to the effects of pure CAPE and CAPE loaded into non-modified micelles. Thus, the higher affinity of CAPE to the modified micelles seems to improve its antioxidant activity. Conclusion CAPE loaded into the micelles having a core segment similar to CAPE, exhibited better protective properties than pure drug in the in vitro model of oxidative stress in endothelial Ea.hy926 cells. The similarity between the drug and micellar core seems to be an effective approach for improvement of its antioxidant activity.