Hybrid pH-sensitive nanoparticles as platforms for delivery of curcumin

Curcumin, the yellow powder derived from the plant Curcuma Longa, exhibited numerous therapeutic applications against wide range of chronic diseases such as diabetes, pancreatitis, arthritis, neurodegenerative diseases and various types of cancer. The mechanism of antineoplastic activity of curcumin is through modulation of cell signaling pathways, mainly blockage of nuclear factor kappa B (NF-κB) activation and induction of apoptosis in different types of human cancer cell lines, associated with excellent safety profile. Unfortunately, the tremendous therapeutic potential of curcumin as a chemopreventive, antineoplastic and chemosensitizing agent has failed to progress towards clinical development and commercialization due to its unfavorable physicochemical properties, low aqueous solubility, chemical instability, and pharmacokinetics. An intriguing strategy to overcome these limitations is the design of nanosized vehicles for efficient delivery of curcumin. The present contribution is focused on elaboration of hybrid pH-sensitive liposomes based on dipalmitoylphosphathydilcholine:cholesterol (DPPC:CHOL) and a pH-sensitive poly(isoprene-b-acrylic acid) (pI-pAA), whereby curcumin is entrapped as a free drug and as a water soluble inclusion complex with polyoxyethylated calix[4]arene, which allows the drug to occupy both the phospholipid membranes and the aqueous core of liposomes. Nanoparticles were characterized by DLS, cryo-TEM, curcumin encapsulation efficacy and in vitro release as a function of pH