期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 154, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.113429
关键词
Solid lipid nanoparticles; Verapamil; Factorial design; Isoproterenol; Myocardial necrosis; Pharmacokinetic
资金
- United Arab Emirates University for the collaborative research [12R104, 12R121]
- AUA-UAEU
- strategic research program of Sheikh Zayed Bin Sultan Center for Health Sciences, United Arab Emirates University, Al Ain, UAE
This research aimed to improve the poor oral bioavailability of Verapamil by using Solid Lipid Nanoparticles (V-SLNs). The optimized V-SLN formulation showed promising results in terms of particle size, entrapment efficiency, and release behavior. In vivo studies demonstrated the cardioprotective effect of V-SLNs and improved pharmacokinetic parameters compared to free drugs.
Verapamil, a calcium channel blocker has poor bioavailability (20-30%) owing to extensive hepatic first-pass metabolism. Hence, the major objective of this research was to improve the oral bioavailability of Verapamil by Solid Lipid Nanoparticles (V-SLNs) using high shear homogenization and ultrasonication technology. A 3(2) factorial design was employed to statistically optimize the formulation to get minimum particle size with maximum entrapment efficiency. The average particle size was 218 nm and the entrapment efficiency was 80.32%. The V-SLN formulation exhibited biphasic behavior with a rapid release at first, then a steady release (75-80%) up to 24 h following the Korsmeyer Peppas release model. In the Isoproterenol induced myocardial necrosis model, oral administration of V-SLNs positively modulated almost all the studied hemodynamic parameters such as left ventricular end-diastolic pressure, cardiac injury markers, and tissue architecture. The cardioprotective effect was also confirmed with histopathological studies. When compared with free drugs, in -vivo pharmacokinetic studies demonstrated a rise in t(1/2), AUC(0-infinity), and Cmax, indicating that bioavailability has improved. These encouraging results demonstrate the promising potential of developed V-SLNs for oral delivery and thereby improve the therapeutic outcome.
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