Minor Project

Minor Project

          My research question is to enhance solubility and stability for increase oral bioavailability of curcumin. Curcumin has not yet been approved as a therapeutic agent, because of its low bioavailability, which is caused by low water solubility and instability in aqueous and basic solutions. There are several methods used nowadays, such as nanoparticles, liposomes, and prodrug method.

        Researchers who have looked at this subject are Parvathy et al. (2010) and Bhawana et al. (2011). They used difference method for increase solubility and stability of curcumin such as prodrug and nanoparticle methods, respectively.

Parvathy et al. (2010) used a prodrug method found that curcumin prodrugs, which are synthesized by conjugation of curcumin with amino acids via ester bond shown solubility and stability in the aqueous higher than curcumin.

Bhawana et al. (2011) used a nanoparticle method found that curcumin nanoparticles had aqueous solubility higher than curcumin but not different in stability.

Debate centers on the basic issue is a prodrug method could increase solubility and stability, whereas nanoparticle method could increase only solubility of curcumin.

My work will be closer to Parvathy’s because I will use a prodrug method for to enhance solubility and stability for increase oral bioavailability of curcumin. A curcumin prodrug, curcumin diglutaric acid, was synthesized by conjugation of curcumin with diglutaric acid via ester bonds. Curcumin diglutaric acid was designed to improve aqueous solubility and enhance chemical stability by comparing with curcumin.

Hopefully my contribution will be to improve aqueous solubility and enhance chemical stability for increase oral bioavailability of curcumin.

Reference List

Parvathy, K. S., Negi, P. S. and Srinivas, P. (2010). Curcumin–amino acid conjugates: Synthesis, antioxidant and antimutagenic attributes. Food Chemistry, 120: 523-530.

Bhawana, Basniwal, R. K., Buttar, H. S., Jain, V.K. and Jain, N. (2011). Curcumin Nanoparticles: Preparation, Characterization, and antimicrobial study. J Agric Food Chem, 59(5): 2056-61.

Assignment 2: Writing an introduction

Water Solubility, Stability and Anticancer Activity of Curcumin and

Curcumin Diglutaric Acid

Stage 1:

To date, a number of phytochemicals have been explored for pharmaceutical applications as therapeutic agents by virtue of their high biological activities. They have been shown to play crucial roles in the pathogenesis of chronic diseases, such as inflammation, atherosclerosis and cancer (Aggarwal & Shishodia, 2006).  One of the extensively investigated plants is Curcuma longa L., called turmeric in English and Kamin-Chan in Thai.

Stage 2:

Tumeric contains turmerin, essential oils and curcuminiods. Commercial curcuminiods contain approximately 77% diferuloylmethane (curcumin), 17% demethoxycurcumin, and 6% bis-demethoxycurcumin. Therefore, curcumin has been identified as the major active component of turmeric extract (Jayaprakasha et al., 2002). Curcumin has been identified as the major active component of turmeric extract and shown to exhibit many pharmaceutical actions such as antioxidant (Ruby et al., 1995; Sabari et al., 2005), anti-inflammatory (Aggarwal et al., 2003; Lantz et al., 2005), and anticancer activities (Sugiyama et al., 1996; Sharma et al., 2005). Various animal models or human studies proved that curcumin is extraordinarily safe even at very high doses uptake (Ringman et al., 2005).

Stage 3:

Despite the fact that its efficacy and safety has been known, curcumin has not yet been approved as a therapeutic agent because of a major problem of its low bioavailability caused by low water solubility and instability in aqueous and basic solutions.  

Stage 4&5:

The objective of this study is an attempt to enhance solubility and stability for increase oral bioavailability of curcumin by using a prodrug methodology. A curcumin prodrug, curcumin diglutaric acid, was synthesized by conjugation of curcumin with diglutaric acid via ester bonds. Curcumin diglutaric acid was designed to have improved aqueous solubility and enhanced chemical stability by comparing with curcumin. Moreover, the anticancer activity of curcumin and curcumin diglutaric acid were also tested against human cancer cell lines such as colon and liver cancer cells.