Posted: June 19, 2006

Nanoparticles overcome solubility limitations of novel anticancer drug

(Nanowerk News) Ovarian cancer is notoriously difficult to treat successfully, largely because drug resistance develops in a majority of patients. Medicinal chemists have responded to the challenge of overcoming drug resistance by creating a new class of drugs, known as tripentones, that show potent activity in tumor cell models but have failed to work in animal models because these compounds are poorly soluble in biological fluids. Now, using a hybrid liposome-nanocapsule, researchers at the Institut National de la Santé et de la Recherche Médicale (INSERM) in Angers, France have developed a lipid nanocapsule that appears to overcome this solubility problem.
The research team, led by Jean-Pierre Benoît, Ph.D., created the lipid nanocapsule using triglycerides and surfactants that self-assemble into a structure that has a water-insoluble core surrounded by a water-soluble shell. When tripentone is added to this mixture it becomes incorporated into the hydrophobic core. The resulting nanoparticles are highly uniform in size at about 50 nanometers in diameter.
By themselves, the tripentone-loaded nanoparticles are so stable that they do not release any drug over three days. However, if empty core-shell nanoparticles are added to the test medium, the drug-loaded nanoparticles release their contents over the course of 10 days. However, drug-loaded nanoparticles alone were highly toxic to tumor cells.
This work is detailed in a paper titled, "Formulation of sustained release nanoparticles loaded with a tripentone, a new anticancer agent." Investigators from the Centre d'Etudes et de Recherche sur le Médicament in Normandy, France, and from the Centre National de la Recherche Scientifique (CNRS) in Monpellier, France, also participated in this study.
Source: National Cancer Institute