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1.
J Biochem Mol Toxicol ; 38(1): e23531, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37724821

RESUMEN

Myocardial infarction (MI) is a common type of ischemic heart disease that affects millions of people worldwide. In recent times, nanotechnology has become a very promising field with immense applications. The current exploration was conducted to synthesize the chitosan-sodium alginate-polyethylene glycol-Ally isothiocyanate nanocomposites (CSP-AIso-NCs) and evaluate their beneficial roles against the isoproterenol (ISO)-induced MI in rats. The CSP-AIso-NCs were prepared and characterized by several characterization techniques. The MI was initiated in the rats by the administration of 85 mg/kg of ISO for 2 days and treated with 10 and 20 mg/kg of CSP-AIso-NCs for 1 month. The changes in heart weight and bodyweight were measured. The cardiac function markers were assessed with echocardiography. The lipid profiles, Na+, K+, and Ca2+ ions, cardiac biomarkers, antioxidant parameters, and inflammatory cytokines were assessed using corresponding assay kits. The histopathological study was done on the heart tissues. The UV spectral analysis revealed the maximum peak at 208 nm, which confirms the formation of CSP-AIso-NCs. The FT-IR analysis revealed the occurrence of different functional groups, and the crystallinity of the CSP-AIso-NCs was proved by the XRD analysis. DLS analysis indicated the size of the CSP-AIso-NCs at 146.50 nm. The CSP-AIso-NCs treatment increased the bodyweight and decreased the HW/BW ratio in the MI rats. The status of lipids was reduced, and HDL was elevated in the CSP-AIso-NCs administered to MI rats. CSP-AIso-NCs decreased the LVEDs, LVEDd, and NT-proBNP and increased the LVEF level. The oxidative stress markers were decreased, and the antioxidants were increased by the CSP-AIso-NCs treatment in the MI rats. The Na+ and Ca+ ions were reduced, and the K+ ions were increased by the CSP-AIso-NCs. The interleukin-1ß and tumor necrosis factor-α were also depleted, and Nrf-2 was improved in the CSP-AIso-NCs administered to MI rats. The histological study revealed the ameliorative effects of CSP-AIso-NCs. Overall, our outcomes revealed that the CSP-AIso-NCs are effective against the ISO-induced MI rats. Hence, it could be a hopeful therapeutic nanomedicine for MI treatment.


Asunto(s)
Quitosano , Infarto del Miocardio , Humanos , Ratas , Animales , Isoproterenol/toxicidad , Quitosano/farmacología , Alginatos/farmacología , Alginatos/metabolismo , Alginatos/uso terapéutico , Polietilenglicoles/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Antioxidantes/metabolismo , Estrés Oxidativo , Iones/metabolismo , Iones/farmacología , Iones/uso terapéutico , Miocardio/metabolismo
2.
Biomed Pharmacother ; 159: 114261, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36689837

RESUMEN

Atherosclerosis is associated with inflammation in the arteries, a significant cause of heart attacks and strokes. Although statin therapy can reduce the chances of atherosclerotic plaque formation, they need to be administered in high doses due to low systemic bioavailability and encountered with side effects. To overcome these challenges, we developed nanoparticles using biocompatible and biodegradable lipids and polymers for improving systemic drug absorption and therapeutic response. The polymeric nanoparticles were prepared using PLGA and PVA, while hybrid nanoparticles were prepared using PLGA and Phospholipon 90 G. Both nanoparticles were systematically optimized by I-optimal response surface design. The optimum formulation composition exhibited particle size of less than 250 nm, polydispersity index of less than 0.3, entrapment efficiency of more than 70%, and sustained drug release up to 6 h. In vivo pharmacokinetic evaluation in rats indicated multi-fold improvement in the extent of drug absorption (Cmax and AUCtotal) for atorvastatin from the nanoparticles vis-à-vis the pure drug suspension. In vivo pharmacodynamic studies also indicated the excellent ability of nanoparticles to lower the elevated levels of lipids (total cholesterol, triglycerides, and low-density lipoproteins) and increase the level of high-density lipoproteins as compared to that of the pure drug suspension.


Asunto(s)
Aterosclerosis , Productos Biológicos , Nanopartículas , Ratas , Animales , Atorvastatina/farmacología , Atorvastatina/uso terapéutico , Ratas Wistar , Portadores de Fármacos/farmacocinética , Lípidos , Polímeros , Liberación de Fármacos , Aterosclerosis/tratamiento farmacológico , Tamaño de la Partícula , Disponibilidad Biológica
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