Systemic delivery of curcumin: 21^st century solutions for an ancient conundrum

Curcumin, a polyphenolic compound derived from the dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, anti-oxidant, anti-proliferative and anti-angiogenic activities. Accumulating experimental evidence suggests that curcumin interferes with a variety of molecular targets and processes involved in cancer. Further, data obtained in multiple preclinical models, as well as in preliminary clinical trials, have documented minimal toxicity of curcumin, even at relatively high doses. However, the clinical advancement of this promising molecule has been hindered by its poor water solubility, short biological half-life, and low bioavailability after oral administration. A variety of approaches are being pursued to overcome these limitations, which include synthesis of curcumin analogues, the use of adjuvants (e.g. piperine), and the development of improved delivery platforms for the parental compound, including liposomal, nanoparticulated and phospholipid complex formulations of curcumin. This review is intended to provide the reader an update on the bioavailability and pharmacokinetic pitfalls of free curcumin, and a comprehensive cataloging of ongoing approaches that have been undertaken to resolve these issues, with the goal of harnessing the true potential of this anti-cancer agent in the clinical arena.