Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: solubility, chemical and photochemical stability

Zein–curcumin composite colloidal particles were synthesized using an antisolvent precipitation method The average particle size could be controlled down to 100–150 nm, depending on the solvent system and the ratio of zein and curcumin used in the synthesis In all cases, spherical particles were obtained, as confirmed by transmission electron microscopy Depending on the preparation conditions, curcumin load and encapsulation efficiency varied from 16 to 41% and 711 to 868%, respectively Solid state characterization by differential scanning calorimetry and X-ray diffraction indicated the amorphous nature of entrapped curcumin An UV irradiation study confirmed enhanced photostability of curcumin due to the entrapment of curcumin in the biopolymeric matrix The particles were also found to have good colloidal stability at a broad range of physiologically relevant pH (12, 45, 67 and 74) and in simulated gastro-intestinal conditions Results from an in vitro mucoadhesion study showed retention of more than 60% curcumin for 150 minutes The mucoadhesion property was further confirmed from a mucin association study carried out on Caco-2 cells

Synthesis and characterisation of zein–curcumin colloidal particles

This review addresses the oncopharmacological properties of curcumin at the molecular level. First, the interactions between curcumin and its molecular targets are addressed on the basis of curcumin's distinct chemical properties, which include H-bond donating and accepting capacity of the β-dicarbonyl moiety and the phenylic hydroxyl groups, H-bond accepting capacity of the methoxy ethers, multivalent metal and nonmetal cation binding properties, high partition coefficient, rotamerization around multiple C-C bonds, and the ability to act as a Michael acceptor. Next, the in vitro chemical stability of curcumin is elaborated in the context of its susceptibility to photochemical and chemical modification and degradation (e.g., alkaline hydrolysis). Specific modification and degradatory pathways are provided, which mainly entail radical-based intermediates, and the in vitro catabolites are identified. The implications of curcumin's (photo)chemical instability are addressed in light of pharmaceutical curcumin preparations, the use of curcumin analogues, and implementation of nanoparticulate drug delivery systems. Furthermore, the pharmacokinetics of curcumin and its most important degradation products are detailed in light of curcumin's poor bioavailability. Particular emphasis is placed on xenobiotic phase I and II metabolism as well as excretion of curcumin in the intestines (first pass), the liver (second pass), and other organs in addition to the pharmacokinetics of curcumin metabolites and their systemic clearance. Lastly, a summary is provided of the clinical pharmacodynamics of curcumin followed by a detailed account of curcumin's direct molecular targets, whereby the phenotypical/biological changes induced in cancer cells upon completion of the curcumin-triggered signaling cascade(s) are addressed in the framework of the hallmarks of cancer. The direct molecular targets include the ErbB family of receptors, protein kinase C, enzymes involved in prostaglandin synthesis, vitamin D receptor, and DNA.

The Molecular Basis for the Pharmacokinetics and Pharmacodynamics of Curcumin and Its Metabolites in Relation to Cancer

The utilization of curcumin as a nutraceutical in food and supplement products is often limited because of its low water solubility, poor chemical stability, and low oral bioavailability. This study examined the impact of pH, storage temperature, and molecular environment on the physical and chemical stability of pure curcumin in aqueous solutions and in oil-in-water emulsions. Unlike naturally occurring curcuminoid mixtures (that contain curcumin, demethoxy-curcumin, and bisdemethoxy-curcumin), pure curcumin was highly unstable to chemical degradation in alkaline aqueous solutions (pH ≥7.0) and tended to crystallize out of aqueous acidic solutions (pH <7). These effects were attributed to changes in the molecular structure of curcumin under different pH conditions. The curcumin crystals formed were relatively large (10–50 μm), which made them prone to rapid sedimentation. The incorporation of curcumin into oil-in-water emulsions (30% MCT, 1 mg curcumin/g MCT, d32 ≈ 298 nm) improved its water dispersibili...

J Karlsen

Papers

Studies on curcumin and curcuminoids. V. Alkaline degradation of curcumin