Novel cure for pancreatic cancer
doi:10.1038/nindia.2012.86 Published online 18 June 2012
Researchers have designed a new kind of nanosized drug carrier that could deliver metformin, an antidiabetic drug to target and kill pancreatic cancer cells. The drug carrier derived from chitosan will be very useful in treating pancreatic cancer.
Pancreatic cancer is difficult to diagnose and treat and has a very high mortality rate. Recent studies have shown that metformin, a widely used anti-diabetic drug could inhibit the growth of pancreatic cancer cells. However, the low bioavailability and short half-life of metformin limits its application as an anticancer drug.
To overcome this, the researchers synthesized O-carboxymethyl chitosan (O-CMC) nanoparticles (NPs) and then trapped metformin within them using calcium chloride. This yielded metformin-incorporated O-CMC NPs. They also prepared bare O-CMC NPs. They carried out drug release, toxicity and biocompatibility studies using both these NPs.
Nearly half of the drug was released from the NPs within the first 10 hours at pH 7.4 and 72% was released after 70 hours. But at acidic pH (pH 4.4), almost 90% of the drug was released within the first hour itself indicating a pH sensitive release of metformin from the NPs.
In toxicity studies with mouse fibroblast cells (normal cells) and pancreatic cancer cells, metformin and and O-CMC-metformin NPs showed 40% more toxicity than bare ones on pancreatic cancer cells. In contrast, the normal cells were not affected by metformin and O-CMC-metformin NPs.
The O-CMC-metformin NPs were also found to be hemocompatible and safe for intravenous administration.
"The O-CMC-metformin nanoparticles with controlled release of metformin at physiological pH can possibly increase metformin's bioavailability decreasing its renal clearance," says lead researcher Vinoth-Kumar Lakshmanan.
The authors of this research are from: Amrita Centre for Nanosciences and Molecular Medicine, and Department of Endocrinology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi, India.
- Snima, K. S. et al. O-Carboxymethyl chitosan nanoparticles for metformin delivery to pancreatic cancer cells. Carbohydr. Polymer. 89, 1003-1007 (2012) | Article |