pH-Sensitive Poly(ethylene glycol)/Poly(ethoxyethyl glycidyl ether) Block Copolymers: Synthesis, Characterization, Encapsulation, and Delivery of a Hydrophobic Drug

Curcumin is a natural polyphenolic compound known for its numerous pharmacological properties. However, its low water solubility and instability at neutral pH are serious drawbacks preventing its use as an oral drug. Well-defined amphiphilic poly(ethylene glycol)-block-poly(ethoxyethyl glycidyl ether) (PEG-b-PEEGE) block copolymers carrying acid-labile acetal groups are synthesized by anionic ring-opening polymerization and investigated as potential pH-sensitive nano-carriers for delivery of curcumin to cancer cells. The nanoparticles, resulting from copolymer self-assembly in aqueous media, are characterized by dynamic light scattering and cryo-transmission electron microscopy. The nanoparticles' stabilities are evaluated in three different phosphate buffers (pH = 7.2, 6.4, and 5.3). The stability decreases at lower pH and a complete disappearance of the nanoparticles is noticed after 4 days at pH 5.3. Curcumin is encapsulated in hydrophobic core of mPEG(40)-b-PEEGE(25) nanoparticles allowing significant enhancements of curcumin solubility in water and lifetime at neutral pH. In vitro curcumin release is studied at different pH by UV-spectroscopy and high-performance liquid chromatography (HPLC). The cytotoxicity of curcumin and curcumin encapsulated in micelles is evaluated by cell viability 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay on MDA-MB-231 human breast cancer cells.