Synthesis of novel biodegradable and self-assembling methoxy poly(ethylene glycol)-palmitate nanocarrier for curcumin delivery to cancer cells

A novel polymeric amphiphile, mPEG-PA, was synthesized with methoxy poly(ethylene glycol) (mPEG) as the hydrophilic and palmitic acid (PA) as the hydrophobic segment. The conjugate prepared in a single-step reaction showed minimal toxicity on HeLa cells. H-1 nuclear magnetic resonance imaging and Fourier transform infrared spectroscopy revealed that the conjugation was through an ester linkage, which is biodegradable. Enzymes having esterase activity, such as lipase, can degrade the conjugate easily, as observed by in vitro studies. mPEG-PA conjugate undergoes self-assembly in an aqueous environment, as evidenced by fluorescence spectroscopic studies with pyrene as a probe. The mPEG-PA conjugate formed micelles in the aqueous solution with critical micelle concentration of 0.12 g l(-1). Atomic force microscopy and dynamic light scattering studies showed that the micelles were spherical in shape, with a mean diameter of 41.43 nm. The utility of mPEG-PA to entrap the potent chemopreventive agent curcumin in the core of nanocarrier was investigated. The encapsulation of a highly hydrophobic compound like curcumin in the nanocarrier makes the drug readily soluble in an aqueous system, which can increase the ease of dosing and makes intravenous dosing possible. Drug-loaded micelle nanoparticles showed good stability in physiological condition (pH 7.4), in simulated gastric fluid (pH 1.2) and in simulated intestinal fluid (pH 6.8). This micellar formulation can be used as an enzyme-triggered drug release carrier, as suggested by in vitro enzyme-catalyzed drug release using pure lipase and HeLa cell lysate. The IC50 of free curcumin and encapsulated curcumin was found to be 14.32 and 15.58 mu M, respectively. (C) 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.