A Silibinin-Poly(ε-Caprolactone) Conjugate as an Enhanced Anticancer Agent.

Abstract

Poly(ε-caprolactone) (PCL) is a hydrolytically degradable biopolyester used in drug delivery to enhance drug solubility and bioavailability, where drugs are typically incorporated physically within the biopolymeric matrix rather than covalently bonded, due to the limited availability of functional groups required for covalent attachment. In pursuit of developing a facile method for the production of a biopolyester-drug covalent conjugate with effective drug loading capacity, this study reports the synthesis of a covalent Silibinin-PCL conjugate (Sil-PCL_Hyd) through a two-step approach. This involves the controlled hydrolysis of a high molecular weight PCL to increase the concentration of carboxylic end groups, which are subsequently used for the catalyzed esterification with Silibinin. The Sil-PCL_Hyd is characterized with mass spectrometry, gel permeation chromatography, thermogravimetric analysis, differential scanning calorimetry, and NMR and UV-vis spectroscopies. The cytotoxic effects of Sil-PCL_Hyd against colorectal adenocarcinoma cells (Caco-2) are measured through the MTT assay. The results of the Sil-PCL_Hyd characterization revealed a Silibinin loading of ≈9.8 wt.%. The MTT assay demonstrated that Sil-PCL_Hyd induced cytotoxic effects at concentrations a hundred times lower than those required for free Silibinin. The proposed approach might represent a reliable pathway for the development of biopolyester-based covalent conjugates with a high drug loading capacity.