Functional block copolymers bearing pendant cinnamyl groups for enhanced solubilization of caffeic acid phenethyl ester

Abstract

The natural bioactive compound caffeic acid phenethyl ester (CAPE) possesses antioxidant, antiinflammatory and anticancer activity. However, the in vivo application of CAPE is limited due to its poor solubility in aqueous media. In this contribution, we report a strategy for enhancing the solubility of CAPE in water by novel micellar carriers comprising segments structurally similar to the CAPE molecule. A series of amphiphilic poly(ethylene oxide)-b-poly(α-cinnamyl-e-caprolactone-co-e-caprolactone)-b-poly(ethylene oxide) (PEO-b-P(CyCL-co-CL)-b-PEO) triblock copolymers were synthesized by combining ring-opening copolymerization and “click” reactions. Calculations of the Flory–Huggins parameter suggested that P(CyCL-co-CL) copolymers have a higher affinity for CAPE than do PCL polymer. Micellar carriers based on PEO-b-P(CyCL-co-CL)-b-PEO were formed via the solvent evaporation method and then loaded with CAPE. Dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo-TEM) revealed the formation of nanosized spherical micelles that maintained their structural integrity upon dilution to 0.055–0.06 g L−1. The main characteristics of the PEO-b-P(CyCL-co-CL)-b-PEO systems were compared to those of the PEO-b-PCL-b-PEO system. The attachment of pendant cinnamyl moieties to the hydrophobic PCL block enhanced the encapsulation efficiency of the micelles and reduced their burst release behavior. Polymeric micelles based on amphiphilic poly(ethylene oxide)-b-poly(e-caprolactone)-b-poly(ethylene oxide)(PEO-b-PCL-b-PEO) triblock copolymers improved the solubility of caffeic acid phenethyl ester (CAPE) in aqueous media. Further on, the grafting of pendant cinnamyl moieties to the PCL block enhanced the compatibility between CAPE and the micellar core, thus increasing the encapsulation efficiency and reducing the burst release effect as compared to those of micelles with an unmodified PCL core.