Nanoparticle encapsulation improves bioavailability of leukemia drug

Busulfan, which belongs to a family of drugs known as alkylating agents, is used to treat hematological malignancies, including chronic myelogenous leukemia.

This drug is given orally, which is normally an advantage but in this case causes problems because the rate at which the drug is absorbed into the bloodstream can vary tremendously from patient to patient. Drug developers have tried a variety of techniques to develop an injectable form of busulfan, but each of these methods has proven less than optimal. Now, however, investigators in France and Belgium have created a nanoparticle that appears to solve these issues and holds the promise of improving the utility of busulfan in cancer therapy.

Reporting its work in the Journal of Biomedical Materials Research Part B: Applied Biomaterials, a team of investigators led by Ruxandra Gref, Ph.D., at Paris-Sud University, in France, describes the variety of polymer nanoparticles that it created in an attempt to find one that would safely encapsulate busulfan and release it in a steady manner into the bloodstream. The two chief challenges the researchers faced were that busulfan is chemically reactive toward many of the materials used to make nanoparticles and that the drug itself tends to form crystals when dissolved in water.

After narrowing their options to five different polymeric nanoparticles, the investigators conducted molecular modeling studies in an attempt to better understand how busulfan would interact with each of the polymers used to make the nanoparticles. Based on these experiments, the researchers chose to use poly(isobutyl cyanoacrylate), or PIBCA, to make busulfan-loaded nanoparticles, which they then showed were able to encapsulate and retain nanocrystalline busulfan efficiently. Release experiments in rat plasma showed that there was an initial burst of drug release followed by a sustained release over six hours. The investigators note that busulfan did not react chemically with the nanoparticle itself.

This work is detailed in a paper titled, “Busulfan loading into poly(alkyl cyanoacrylate) nanoparticles: Physico-chemistry and molecular modeling.” Investigators from the Université Catholique de Louvain, in Brussels, Belgium, and Ethypharm, in Saint-Cloud, France, also participated in this study. This paper was published online in advance of print publication. An abstract is available through PubMed. View abstract.