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Numerous selleckbio epidemiological, clinical, and laboratory studies have suggested that ibuprofen, a commonly used nonsteroidal anti-inflammatory drug, inhibits the promotion and proliferation of some tumors.1�C8 Recently, we demonstrated the antiproliferative effects of ibuprofen on the human gastric cancer cell line MKN-45.9 Ibuprofen, at concentrations of 400�C800 ��M, significantly inhibited cellular proliferation in a time- and concentration-dependent manner. Using microarray technology, we studied changes in gene expression profiles after ibuprofen treatment, over time. Ibuprofen exerted its antiproliferative actions through cell-cycle control and the induction of apoptosis. However, high doses of ibuprofen were required to elicit these antiproliferative effects.
When we used lower concentrations of ibuprofen (<400 ��M), there were no evident effects on cell proliferation. In recent years, nanoparticles (NPs) have piqued the interest of the medical community for use in cancer diagnosis and treatment, and as delivery vectors for biologic or pharmacologic agents.10�C13 One of the advantages of NPs is that water-insoluble therapeutics can be transported more efficiently in the aqueous physiological environment when formed into stable NPs.14 Ibuprofen is a propionic acid derivative that has the disadvantage of low water solubility. Over the years, a variety of natural and synthetic polymers have been explored for the preparation of NPs; specifically, poly(lactic acid), poly(glycolic acid), and their copolymer, poly(lactic-co-glycolic acid) (PLGA), have been extensively investigated because of their biocompatibility and biodegradability.
PLGA particles, in particular, have been widely studied as therapeutic delivery vehicles because they are biodegradable15 and biocompatible.16�C18 Some study has been undertaken to investigate hydrophobic drug incorporation into PLGA NPs.19,20 Because of their hydrophobic nature, it is relatively easy to entrap hydrophobic drugs into PLGA NPs. Polymeric NPs have advantages with respect to other drug delivery systems, such as greater stability during storage.21 Biodegradable NPs made from PLGA have been extensively used as drug delivery systems for a variety of drugs.
22,23 PLGA microparticles are already approved for establishing the sustained release of leuprolide (Lupron Depot?, Abbott Laboratories, IL) and triptorelin (Trelstar?, Watson Pharmaceuticals, Parsipanny, NJ) in cancer therapy. In a previous study, Cilengitide we analyzed the gene expression profiles of MKN-45 cells treated with free ibuprofen at various concentrations and over a time course.9 We observed that after 24 hours of treatment, Angiopoietin-like protein 4 (ANGPTL4) was upregulated and the expression levels were dependent on ibuprofen concentration (data not shown).