Encapsulating Childhood Leukemia Drugs in Nanoparticles Diminishes Toxic Side Effects

Cancer researchers have demonstrated that highly toxic chemotherapy agents used to treat childhood leukemia could be safely administered in much lower effective doses when the drugs were encapsulated in polymer nanoparticles.

Investigators at the University of Delaware (Wilmington, USA) prepared polymeric nanoparticles with an average diameter of 110 nanometers from an amphiphilic block copolymer of poly(ethylene glycol) (PEG) and poly(epsilon-caprolactone) (PCL) bearing pendant cyclic ketals (ECT2). These nanoparticles were not toxic when added to cultured cells in vitro or administered to mice in vivo. Studies using nanoparticles labeled with fluorescent dyes revealed leukemic cell surface binding and internalization. In vivo biodistribution studies showed accumulation of nanoparticles in the liver and spleen with subsequent clearance of the particles with time.

The investigators prepared nanoparticles with encapsulated dexamethasone (Dex), one of the most common chemotherapeutic drugs used in the treatment of childhood leukemia. While Dex and similar drugs produce five-year survival rates for juvenile acute lymphoblastic leukemia (ALL) patients approaching 90%, the deleterious side effects of these drugs, including secondary cancers and fertility, cognitive, hearing, and developmental problems, raise significant quality of life issues.

Results of studies with encapsulated Dex published in the November 29, 2012, online edition of the journal Molecular Pharmaceutics revealed that encapsulation of Dex into the nanoparticles (Dex-NP) did not compromise the bioactivity of the drug. Dex-NPs induced glucocorticoid phosphorylation and showed cytotoxicity similar to free Dex in leukemic cells. In a preclinical model of leukemia, Dex-NPs significantly improved the quality of life and survival of mice as compared to the free drug.

"There are currently seven or eight drugs that are used for chemotherapy to treat leukemia in children," said senior author Dr. A. K. Rajasekaran, professor of biological sciences at the University of Delaware. "They are all toxic and do their job by killing rapidly dividing cells. However, these drugs do not differentiate cancer cells from other, healthy cells. The good news is that these drugs are 80%–90% effective in curing leukemia. The bad news is that many chemotherapeutic treatments cause severe side effects, especially in children. Encapsulating the drug uses one third of the typical dose, with good treatment results and no discernible side effects. In addition, the mice that received the drugs delivered via nanoparticles survived longer than those that received the drug administered in the traditional way."

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