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1.
Regul Toxicol Pharmacol ; 81: 316-321, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27664321

RESUMO

This study determined whether meloxicam in nanocapsules modifies stomach and liver damage caused by free meloxicam in mice. Male Swiss mice were treated with blank nanocapsules or meloxicam in nanocapsules or free meloxicam (10 mg/kg, intragastrically, daily for five days). On the seventh day, blood was collected to determine biochemical markers (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, total bilirubin, unconjugated bilirubin, albumin and alkaline phosphatase). Stomachs and livers were removed for histological analysis. There was no significant difference in the biochemical markers in the plasma of mice. Meloxicam in nanocapsules did not have an ulcerogenic potential in the stomach or cause lipid peroxidation in the stomach and liver. Free meloxicam increased the ulcerogenic potential in the stomach and lipid peroxidation in the stomach and liver. Meloxicam in nanocapsules caused less histological changes than free meloxicam. In conclusion, polymeric nanocapsules can represent a technological alternative to reduce the toxicity caused by meloxicam.


Assuntos
Caproatos/farmacologia , Lactonas/farmacologia , Fígado/efeitos dos fármacos , Nanocápsulas/química , Polissorbatos/farmacologia , Estômago/efeitos dos fármacos , Tiazinas/antagonistas & inibidores , Tiazóis/antagonistas & inibidores , Animais , Peso Corporal/efeitos dos fármacos , Caproatos/administração & dosagem , Caproatos/química , Relação Dose-Resposta a Droga , Mucosa Gástrica/metabolismo , Lactonas/administração & dosagem , Lactonas/química , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Meloxicam , Camundongos , Nanocápsulas/administração & dosagem , Tamanho do Órgão/efeitos dos fármacos , Polissorbatos/administração & dosagem , Polissorbatos/química , Estômago/patologia , Relação Estrutura-Atividade , Tiazinas/administração & dosagem , Tiazinas/toxicidade , Tiazóis/administração & dosagem , Tiazóis/toxicidade
2.
Eur J Pharm Biopharm ; 86(2): 167-77, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23643792

RESUMO

Polymeric nanocarriers have shown great promise as delivery systems. An alternative strategy has been to explore new delivery routes, such as intradermal (i.d.), that can be used for vaccines and patch-based drug delivery. Despite their many advantages, there are few toxicity studies, especially in vivo. We report a safety assessment of biodegradable poly(ɛ-caprolactone) lipid-core nanocapsules (LNC) with a mean size of 245±10nm following single and repeated intradermal injections to Wistar rats. Suspensions were prepared by interfacial deposition of polymer. The animals (n=6/group) received a single-dose of saline solution (1.2ml/kg) or LNC (7.2×10(12)LNC/kg), or repeated-doses of two controls, saline solution or Tween 80 (0.9ml/kg), or three different concentrations of LNC (1.8, 3.6, and 5.4×10(12)LNC/kg) for 28 consecutive days. Clinical and physiological signs and mortality were observed. Samples of urine, blood, and tissue were used to perform toxicological evaluation. There were no clinical signs of toxicity or mortality, but there was a slight decrease in the relative body weights in the Tween 80-treated group (p<0.01) after repeated administration. No histopathological alterations were observed in tissues or significant changes in blood and urinary biomarkers for tissue damage. Mild alterations in white blood cells count with increases in granulocytes in the Tween-80 group (p<0.05) were found. Genotoxicity was evaluated through the comet assay, and no statistical difference was observed among the groups. Therefore, we conclude that, under the conditions of these experiments, biodegradable LNC did not present appreciable toxicity after 28 consecutive days of intradermal administration and is promising for its future application in vaccines and patch-based devices for enhancing the delivery of drugs.


Assuntos
Nanocápsulas/administração & dosagem , Nanocápsulas/efeitos adversos , Polímeros/administração & dosagem , Polímeros/análise , Animais , Caproatos/administração & dosagem , Caproatos/efeitos adversos , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/efeitos adversos , Sistemas de Liberação de Medicamentos/métodos , Granulócitos/efeitos dos fármacos , Injeções Intradérmicas/métodos , Lactonas/administração & dosagem , Lactonas/efeitos adversos , Lipídeos/administração & dosagem , Lipídeos/efeitos adversos , Masculino , Tamanho da Partícula , Polissorbatos/administração & dosagem , Polissorbatos/efeitos adversos , Ratos , Ratos Wistar , Suspensões/administração & dosagem , Suspensões/efeitos adversos
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