Curcumin-encapsulated MePEG/PCL diblock copolymeric micelles: a novel controlled delivery vehicle for cancer therapy

Abstract

Aim: To develop a suitable formulation of curcumin-encapsulated methoxy poly(ethylene glycol) (MePEG)/poly-ε-caprolactone (PCL) diblock copolymeric micelle by varying the copolymer ratio, for achieving small sized micelles with high encapsulation of curcumin. To evaluate the micelle’s aqueous solubility and stability, efficiency of cellular uptake, cell cytotoxicity and ability to induce apoptosis on pancreatic cell lines. Method: Amphiphilic diblock copolymers (composed of MePEG and PCL) were used in various ratios for the preparation of curcumin-encapsulated micelles using a modified dialysis method. Physicochemical characterization of the formulation included size and surface charge measurement, transmission electron microscopy characterization, spectroscopic analysis, stability and in vitro release kinetics studies. The anticancer efficacy of the curcumin-encapsulated micelle formulation was compared with unmodified curcumin in terms of cellular uptake, cell cytotoxicity and apoptosis of pancreatic cell lines MIA PaCa-2 and PANC-1. Results: Physiochemical characterization of the formulations revealed that curcumin was efficiently encapsulated in all formulation of MePEG/PCL micelles; however, a 40:60 MePEG:PCL ratio micelle was chosen for experimental studies owing to its high encapsulation (∼60%) with size (∼110 nm) and negative ζ potential (∼-16 mV). Curcumin-encapsulated micelles increased the bioavailability of curcumin due to enhanced uptake (2.95 times more compared with unmodified) with comparative cytotoxic activity (by induction of apoptosis) compared with unmodified curcumin at equimolar concentrations. IC50 values for unmodified curcumin and curcumin micelles were found to be 24.75 µM and 22.8 µM for PANC-1 and 14.96 µM and 13.85 µM for MIA PaCa-2, respectively. Together the results clearly indicate the promise of a micellar system for efficient solubilization, stabilization and controlled delivery of the hydrophobic drug curcumin for cancer therapy.