Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Biol Trace Elem Res ; 201(3): 1344-1357, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35499800

RESUMO

Current study was aimed to investigate the ability of L.acidophilus SNZ 86 to biotransform inorganic selenium to a more active organic form, resulting in trace element enrichment. Selenium-enriched L. acidophilus SNZ 86 has been shown to be effective in the treatment of a variety of gastrointestinal illnesses, indicating the need for additional research to determine the full potential of this therapeutic strategy in the treatment of metabolic disorders. Herein, we employed the western style diet-induced model of non-alcoholic fatty liver disease (NAFLD) to explore the therapeutic effect of selenium-enriched probiotic (SP). Male Sprague Dawley rats (160-180 g) were fed a high-fat (58% Kcal of fat) and high-fructose (30% w/v) diet for 12 weeks to develop an animal model mimicking NAFLD. High-fat and High-fructose diet-fed rats exhibited hyperglycemia, hyperlipidemia, insulin resistance, abnormal liver function test, increased hepatic oxidative stress, and steatosis. SP was then administered orally (L acidophilus 1 × 109 CFU/ml containing 0.4 g Se/day; p.o.) for 8 weeks. The selenium enrichment within L. acidophilus SNZ 86 was validated by TEM, which allowed for visualisation of the selenium deposition and size distribution in the probiotic. In NAFLD control rats, the expression of autophagy proteins (LC-3 A/B and Beclin), AMPK, and SIRT-1 was significantly reduced indicating downregulation of autophagy. However, supplementation of SP ameliorates hepatic steatosis as evidenced by improved biochemical markers and autophagic activation via upregulation of the AMPK and SIRT-1 pathway showing the relevance of autophagy in the disease aetiology. Collectively, these findings provide us with a better understanding of the role of SP in the treatment of hepatic steatosis and establish a therapeutic basis for potential clinical application of SP in the prevention of NAFLD and associated pathological conditions.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Probióticos , Selênio , Ratos , Masculino , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Selênio/metabolismo , Proteínas Quinases Ativadas por AMP , Dieta Ocidental/efeitos adversos , Ratos Sprague-Dawley , Fígado/metabolismo , Metabolismo dos Lipídeos , Probióticos/farmacologia , Autofagia , Frutose/farmacologia , Dieta Hiperlipídica/efeitos adversos
2.
Int J Pharm ; 622: 121827, 2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-35589006

RESUMO

In the current work, we aimed to deliver high dose of voriconazole (VRC) to lung through dry powder for inhalation (DPIs). Furthermore, the research tested the hypothesis that drug nanocrystals can escape the clearance mechanisms in lung by virtue of their size and rapid dissolution. High dose nanocrystalline solid dispersion (NCSD) based DPI of VRC was prepared using a novel spray drying process. Mannitol (MAN) and soya lecithin (LEC) were used as crystallization inducer and stabilizer, respectively. The powders were characterized for physicochemical and aerodynamic properties. Chemical interactions contributing to generation and stabilization of VRC nanocrystals in the matrix of MAN were established using computational studies. Performance of NCSD (VRC-N) was compared with microcrystalline solid dispersion (VRC-M) in terms of dissolution, uptake in A549 and RAW 264.7 cells. Plasma and lung distribution of VRC-N and VRC-M in Balb/c mice upon insufflation was compared with the intravenous product. In VRC-N, drug nanocrystals of size 645.86 ± 56.90 nm were successfully produced at VRC loading of 45%. MAN created physical barrier to crystal growth by interacting with N- of triazole and F- of pyrimidine ring of VRC. An increase in drug loading to 60% produced VRC crystals of size 4800 ± 200 nm (VRC-M). The optimized powders were crystalline and showed deposition at stage 2 and 3 in NGI. In comparison to VRC-M, more than 80% of VRC-N dissolved rapidly in around 5-10 mins, therefore, showed higher and lower drug uptake into A549 and RAW 264.7 cells, respectively. In contrast to intravenous product, insufflation of VRC-N and VRC-M led to higher drug concentrations in lung in comparison to plasma. VRC-N showed higher lung AUC0-24 due to escape of macrophage clearance.


Assuntos
Inaladores de Pó Seco , Manitol , Administração por Inalação , Aerossóis/química , Animais , Humanos , Manitol/química , Camundongos , Tamanho da Partícula , Pós , Voriconazol
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA