IIT Mandi researchers find way to incorporate turmeric-derived curcumin into drug nanoformulations

Mandi: Researchers from Indian Institute of Technology Mandi and Indian Association for the Cultivation of Science, Kolkata, have developed a new route by which curcumin, the medicinal chemical present in turmeric, can be incorporated into drug nanoformulations. Their work has recently been published in an international journal, Crystal Growth & Design. It is a peer-reviewed scientific journal published by the American Chemical Society.

The research team consists of Dr. Prem Felix Siril, Principal Investigator of the research and Associate Professor, School of Basic Sciences, IIT Mandi, and his research scholar Ms. Kajal Sharma, along with Dr. Bidisha Das from the Indian Association for the Cultivation of Science, Kolkata.

Turmeric has been used as a food item in India for centuries, not merely as a condiment but also as a medicinal material. Curcumin, a low-molecular-weight compound present in turmeric, has been reported to be the active medicinal principle because of its antioxidant, anti-inflammatory, antiproliferative (tending to inhibit cell growth) and antiangiogenic (refers to pertaining to a substance that reduces the growth of new blood vessels needed by tumors) properties. Thus, curcumin is considered a potential drug for a variety of illnesses including cancer, cardiovascular problems and neurodegenerative disorders.

Despite promise and the extensive use of turmeric in alternative and lifestyle therapies, the development of mainstream drugs based on curcumin has been hindered by a few problems. Curcumin, in its natural form, is insoluble in water, which makes it less bioavailable and hence difficult for the drug to reach the tissues and cells in which they are needed. Furthermore, free curcumin is unstable; it is susceptible to fragmentation with time, especially in neutral medium. This leads to loss of efficacy of the drug. Thus, the incorporation of curcumin in drugs depends on increasing the water solubility of the compound and enhancing its stability and bioavailability.

Dr. Siril and his team identified the reason for the water insolubility of curcumin. “Curcumin, in its natural crystalline form, is poorly soluble in water”, he explains. Solid-state phase transformation of such molecules to the relatively less stable and more aqueous soluble amorphous form is a well-adapted formulation technique in pharmaceutical research.

“But the solution is not as simple as that. Amorphous materials tend to crystallise over time, which brings back the original problem”, attests Dr. Siril. To overcome this, the IIT Mandi team combined two approaches.

The researchers used Indomethacin, a well-known nonsteroidal anti-inflammatory drug to precipitate along with curcumin in order to stabilize it in amorphous form. The combination is expected to have the therapeutic benefits of both curcumin as well as Indomethacin.

Additionally, they coated each tiny particle (nanoparticle) of Co-amorphous curcumin and indomethacin with a natural polymer called chitosan, which is extracted from shells of shrimps and other crustaceans. The chitosan generate a hydrophobic (water repellent) covering around curcumin nanoparticles and prevent it from sticking to each other and forming crystals.

“These two approaches improve two major problems “aqueous stability and solubility” of curcumin and introduce an additional pH (Potential of Hydrogen) responsive release behaviour to the formulation. This is expected to increase the chances of direct nanoparticle absorption through the intestine after oral intake and safe delivery of curcumin to the required site with minimal aqueous exposure. The formulation did not recrystalise even after a whole year”, says Ms. Kajal. These effects have been found to be a result of the intermolecular interactions between the curcumin, indomethacin and chitosan.

“Our research shows that curcumin can indeed be incorporated into stable drug formulations for better therapeutic efficacy”, says Dr. Siril, on the implications of their findings.