Advanced drug delivery systems of curcumin for cancer chemoprevention

Abstract

Since ancient times, chemopreventive agents have been used to treat/prevent several diseases including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, antioxidant, antiproliferative, anticarcinogenic, and antiangiogenic activity in various cell cultures and some animal studies. Research over the past 4 decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been shown to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician's armamentarium.

Figure 1

Structures of the three curcuminoids as components of curcumin.

Figure 2

Atomic force microscopy (AFM) image of curcumin-loaded PLGA nanoparticles prepared by emulsion-diffusion-evaporation method (From shaikh et al., reproduced with permission) (37).

Figure 3

Confocal scanning images of bone marrow, spleen and liver tissues of rats after 6 h of intravenous administration of curcumin vesicles (CmVe) and curcumin lipid nanospheres (CmLn). Yellow flourescence shows the presence of curcumin in the tissues (From Sou et al., reproduced with permission) (74).

Figure 4

(a) shows photographs of blank implants and of curcumin implants. (b) In Vitro release of curcumin from a 2-cm implant (3.4 mm diameter; 200 mg) with 10% curcumin load (n=3). (c) In vivo release of curcumin from a 2-cm implant formulated either with 10% or 20% curcumin load (n=3). Implants were grafted subcutaneously at the back of Sprague-Dawley rats and were recovered at the time of euthanasia at indicated times to measure the residual curcumin content. Cumulative release was calculated by subtracting residual amount at each interval from initial amount of drug present in implants (reproduced with permission from data published by Bansal et al.) (10).