RESUMO
AIM: The present work aimed at the DIM-loaded microparticles development and anti-hypernociceptive action evaluation. METHOD: The formulations were prepared by O/W solvent emulsion-evaporation method and characterised by particle diameter, content and DIM encapsulation efficiency, drug release profile, thermal behaviour and physicochemical state. The anti-hypernociceptive action was evaluated in the animal model of acute inflammatory pain. RESULT: The MPs had a mean diameter in the micrometric range (368 ± 31 µm), narrow size distribution, DIM content of 150 mg/g, encapsulation efficiency around 84% and prolonged compound release. Evaluations of the association form of DIM to MPs demonstrated the feasibility of the systems to incorporate DIM and increases its thermal stability. An improvement in the anti-hypernociceptive action of DIM was observed by its microencapsuation, because it was increased and prolonged. CONCLUSION: Therefore, the MPs developed represent a promising formulation for oral administration of the DIM in the treatment of inflammatory pain.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Celulose/análogos & derivados , Portadores de Fármacos/química , Indóis/administração & dosagem , Dor/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Cápsulas , Celulose/química , Indóis/uso terapêutico , Masculino , CamundongosRESUMO
This study aimed to characterize the physicochemical properties of 3,3'-diindolylmethane (DIM)-loaded nanocapsules (NCs) as well as the antinociceptive effect using distinct animal models (hot plate test, formalin-induced nociception and complete Freud's adjuvant induced paw inflammation). The DIM-loaded NCs (composed by primula oil and ethylcellulose) were characterized using differential scanning calorimetry, thermogravimetric analysis, Fourier-transformed infrared spectroscopy, X-ray diffractometry and scanning electron microscopy. The physicochemical characterization demonstrated that DIM could be molecularly dispersed into the NCs, whose size was nanometric with a spherical shape. An improvement in DIM thermal stability was achieved by its encapsulation and there were no interactions among the formula components. For the nociceptive evaluation, male adult Swiss mice were pretreated with the NCs or free DIM by the intragastric route at the dose of 10â¯mg/Kg (time-response curve), 5 or 2.5â¯mg/Kg (dose-response curve). The behavioral tests were performed over an experimental period of 0.5-8â¯h. Both free and nanoencapsulated DIM reduced the mechanical hypernociception induced by CFA, mitigated nociceptive behavior of formalin-induced neurogenic and inflammatory pain and increased paw withdrawal latency assessed by the hot-plate test. Importantly, the DIM nanoencapsulation promoted a rapid initiation and prolonged the bioactive antinociceptive action (up to 8â¯h) as well as reduced the effective dose in comparison to its free form. In summary, this study reported that the NCs had adequate nanometric size, increased DIM stability and its antinociceptive action in different animal models, suggesting that the formulation may be a possible therapeutic alternative to the management of pain and inflammatory-related pathologies.
Assuntos
Analgésicos/farmacologia , Edema/tratamento farmacológico , Indóis/farmacologia , Inflamação/tratamento farmacológico , Nanocápsulas/química , Analgésicos/química , Animais , Físico-Química , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Formaldeído , Adjuvante de Freund , Indóis/química , Inflamação/induzido quimicamente , Masculino , Camundongos , Medição da Dor , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
NEW FINDINGS: What is the central question of this study? Monosodium glutamate causes cognitive impairment. Does resistance exercise improve the performance of rats treated with monosodium glutamate? What is the main finding and its importance? Resistance exercise is effective against monosodium glutamate-induced memory impairment in male and female rats. Monosodium glutamate (MSG), a flavour enhancer in diets, causes cognitive impairment in rodents. Exercise has been reported to protect against impairment of memory in humans. In this study, we investigated whether resistance exercise improves the performance of male and female rats treated with MSG in tests of memory and motor co-ordination. Wistar rats received MSG [4 g (kg body weight)-1 day-1 , s.c.] from postnatal day 1 to 10. At postnatal day 60, the animals started a resistance exercise protocol in an 80 deg inclined vertical ladder apparatus and performed it during 7 weeks. Rats performed object recognition and location memory tests. Resistance exercise reduced impairment in motor co-ordination of male and female rats treated with MSG. Resistance exercise was effective against the decrease in exploratory preference in the long-term recognition memory for novel objects of male rats treated with MSG. In MSG-treated female rats, resistance exercise was effective against the decrease in exploratory preference in the novel object location test. The exploratory preference of female rats in the long-term recognition memory test was similar in all groups. The short-term memory was not altered by MSG or resistance exercise in male and female rats. This study demonstrates that MSG affected the memory of male and female rats in different ways. Resistance exercise was effective against the decrease in recognition for male rats and in location memory for female rats treated with MSG. This report demonstrates the beneficial effects of resistance exercise against the prejudice of motor condition and impairment of memory induced by MSG in male and female rats.
Assuntos
Peso Corporal/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Glutamato de Sódio/farmacologia , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Feminino , Masculino , Condicionamento Físico Animal/métodos , Ratos WistarRESUMO
Organoselenium compounds have been targeted to new therapeutic tools development due to their pharmacological actions. However, some toxicity issues and physicochemical limitations delay the clinical application of these compounds. The incorporation of organoselenium molecules into nanostructured systems arises as a promising alternative to overcome such restrictions. The current study proposed the characterization of the polymeric nanocapsules of p,p'-methoxyl-diphenyl diselenide [(OMePhSe)2] as well as the evaluation of the in vivo toxicity and biodistribution profile. The nanocapsules, which were composed by medium-chain triglycerides as the oil core and poly(ε-caprolactone) as the polymeric wall, showed nanometric size (236±4), low polydispersity (<0.2), negative zeta potential (-5.4±0.06), neutral pH values (7.2±0.08) and a high encapsulation efficiency (98%). Besides, the nanoencapsulation process increased the (OMePhSe)2 stability. The repeated intragastric administration of (OMePhSe)2 nanoencapsulated (25mg/kg/day during 7days) did not cause any alteration in the oxidative status, hematological parameters, and plasma biochemical markers of cellular damage. Moreover, the (OMePhSe)2 incorporation into nanocapsules increased the selenium concentrations in the tissues (kidneys, liver and plasma) suggesting an improvement in its oral bioavailability.
Assuntos
Portadores de Fármacos/química , Nanocápsulas/química , Compostos Organosselênicos/química , Polímeros/química , Animais , Portadores de Fármacos/toxicidade , Estabilidade de Medicamentos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Masculino , Camundongos , Nanocápsulas/toxicidade , Compostos Organosselênicos/toxicidade , Polímeros/toxicidade , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologia , Testes de Toxicidade Aguda/métodosRESUMO
Major depressive disorder is the most severe and debilitating disease among psychiatric illnesses. The abrupt interruption of antidepressant treatment may lead to a complex physiological and neuropsychiatric syndrome. The organoselenium compound (MeOPhSe)2 has been reported to have neuroprotective properties in animal models. The study aimed to investigate the effects of single or repeated administration of (MeOPhSe)2 on depressive-like behavior and if the compound administration, and its discontinuation, may affect the anxiolytic-like phenotype in Swiss mice. The results showed that repeated intragastric administration of (MeOPhSe)2 (dose range: 0.1-5mg/kg), different from a single administration, reduced the immobility time in the mouse tail suspension test. A single administration of (MeOPhSe)2 at a dose of 5mg/kg decreased the immobility time, increased the swimming time and did not alter the climbing behavior in the modified forced swimming test (mFST). Repeated administration of (MeOPhSe)2 decreased the immobility time, did not alter the swimming time and increased the climbing behavior in the mouse mFST. Repeated administration of (MeOPhSe)2 at a dose of 5mg/kg elicited a mouse anxiolytic-like phenotype in the elevated plus maze and light-dark tests. Markers of hepatic and renal function tests were not altered by repeated administration of (MeOPhSe)2 to mice. The findings indicate that a single or repeated administration of (MeOPhSe)2 elicited an antidepressant-like action in mice. Moreover, repeated treatment with (MeOPhSe)2 produced an anxiolytic-like action in mice and its profile remained stable after discontinuation.