Enhanced apoptotic effects of dihydroartemisinin-aggregated gelatin and hyaluronan nanoparticles on human lung cancer cells.

Department of Biomedical Engineering, I-Shou University, Kaohsiung, TaiwanReceived 8 June 2013; revised 31 July 2013; accepted 10 August 2013Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.b.33023Abstract: Recent studies suggest that dihydroartemisinin(DHA), a derivative of artemisinin isolated from the traditionalChinese herb Artemisia annua L., has anticancer properties.Due to poor water solubility, poor oral activity, and a shortplasma half-life, large doses of DHA have to be injected toachieve the necessary bioavailability. This study examinedincreasing DHA bioavailability by encapsulating DHA withingelatin (GEL) or hyaluronan (HA) nanoparticles via an electro-static field system. Observations from transmission electronmicroscopy show that DHA in GEL and HA nanoparticlesformed GEL/DHA and HA/DHA aggregates that were approxi-mately 30–40 nm in diameter. The entrapment efficiencies forDHA were approximately 13 and 35% for the GEL/DHA andHA/DHA aggregates, respectively. The proliferation of A549cells was inhibited by the GEL/DHA and HA/DHA aggregates.Fluorescent annexin V-fluorescein isothiocyanate (FITC) andpropidium iodide (PI) staining displayed low backgroundstaining with annexin V-FITC or PI on DHA-untreated cells. Incontrast, annexin V-FITC and PI stains dramatically increasedwhen the cells were incubated with GEL/DHA and HA/DHAaggregates. These results suggest that DHA-aggregated GELand HA nanoparticles exhibit higher anticancer proliferationactivities than DHA alone in A549 cells most likely due to thegreater aqueous dispersion after hydrophilic GEL or HAnanoparticles aggregation. These results demonstrate thatDHA can aggregate with nanoparticles in an electrostatic fieldenvironment to form DHA nanosized aggregates.