All-trans-retinoic acid release from core-shell type nanoparticles of poly (ε-caprolactone)/poly (ethylene glycol) diblock copolymer

Poly(E-caprolactone)/poly(ethylene glycol) (abbreviated as CE) diblock copolymers were synthesized to make core-shell type nanoparticles for all-trans-retinoic acid (atRA). Fluorescence spectroscopy showed that critical association concentration (CAC) value decreased at higher MW of CE diblock copolymer. Drug loading characteristics were studied under various experimental conditions. Drug contents and loading efficiency increased as the MW of poly(E-caprolactone) (PCL) block of CE and initial drug feeding amount increased. Solvent used and preparation method also affected drug contents and loading efficiency. According to H-1 NMR using CDCl3 and D2O, specific peaks of the PCL block and drug appearing in CDCl3, disappeared at D2O, suggesting hydrophobic core with hydrophilic shell formed in water. atRA release was faster at smaller MW of copolymer and lower drug contents. Nanoparticles prepared in DMF showed faster release rate compared with those prepared in THF or acetone. Cytotoxicity of atRA against U87MG, U251MG and U343MG cell lines were increased by nanoencapsulation while empty nanoparticles of CE diblock copolymer were not significantly affected. (C) 2004 Elsevier B.V. All rights reserved.