title: Improvement of the inhibitory effect of xanthones on NO production by encapsulation in PLGA nanocapsules.
abstract: For the first time the inhibitory effect of xanthone and 3-methoxyxanthone on nitric oxide (NO) production by IFN-gamma/LPS activated J774 macrophage cell line is reported. A remarkable improvement of this effect promoted by encapsulation of these compounds in nanocapsules of poly (DL-lactide-co-glycolide) (PLGA) is also demonstrated. A weak inhibitory effect of 3.6% on NO production by activated macrophages was observed for xanthone at the highest studied concentration (100 microM). This effect was slightly higher for 3-methoxyxanthone at the same concentration, producing a reduction of 16.5% on NO production. In contrast, equivalent concentrations of xanthone and 3-methoxyxanthone incorporated in nanocapsules produced a significant decrease on NO production of 91.8 and 80.0%, respectively. Empty nanocapsules also exhibited a slight NO inhibitory activity, which may be due to the presence of soybean lecithin in the composition of the nanosystems. The viability of the macrophages was not affected either by free or nanoencapsulated xanthones. Fluorescence microscopy analysis confirmed that a phagocytic process was involved in the macrophage uptake of xanthone- and 3-methoxyxanthone-loaded PLGA nanocapsules. Phagocytosis might be the main mechanism responsible for the enhancement of the intracellular delivery of both compounds and consequently for the improvement of their biological effect.
authors.affiliation: CEQOFFUP--Centro de Estudos de Química Orgânica, Fitoquímica e Farmacologia da Universidade do Porto, Faculdade de Farmácia, Universidade do Porto, R. Aníbal Cunha, 164, 4050-047 Porto, Portugal.
authors.forename: Maribel
authors.initials: M
authors.lastname: Teixeira
authors.forename: Fátima
authors.initials: F
authors.lastname: Cerqueira
authors.forename: Carlos Maurício
authors.initials: CM
authors.lastname: Barbosa
authors.forename: Maria São José
authors.initials: MS
authors.lastname: Nascimento
authors.forename: Madalena
authors.initials: M
authors.lastname: Pinto
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D049329:Nanostructures; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000032:analysis; D009599:Nitroprusside / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D044004:Xanthones / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D004337:Drug Carriers; D020030:Nitric Oxide Donors; D009573:Nitrites; D011108:Polymers; D044004:Xanthones; D009599:Nitroprusside; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D009569:Nitric Oxide; D019344:Lactic Acid