Encapsulation of Carvedilol in Nanomicelles Improves Central Hemodynamics and Target Organ Damage Protection in Spontaneously Hypertensive Rats.

Abstract

The hypothesis of this work was that chronic treatment with carvedilol (CAR) administered in a nanomicelles-based formulation (CAR-NMs), which increases CAR oral bioavailability, is more effective than a conventional liquid CAR formulation (CAR-LCF) and is comparable to chronic treatment with losartan (LOS) in improving hemodynamic parameters and preventing target organ damage (TOD) in spontaneously hypertensive (SH) rats. Chronic treatment with CAR-NMs significantly improved central hemodynamic parameters (systolic and diastolic blood pressure (BP) and its variability) to a similar extent as LOS, and with superior efficacy than CAR-LCF. Although LOS was more effective than CAR-NMs and CAR-LCF in reducing peripheral systolic BP, both LOS and CAR-NMs, in contrast to CAR-LCF, were able to significantly reduce short-term BP variability indexes. Both CAR formulations and LOS significantly reduced aortic media wall thickness and interstitial collagen deposition, and lowered TNF-α expression in left ventricle (LV) in SH rats. Only CAR-NMs significantly reduced IL-6 expression and were more effective in reducing ventricular TGF-β expression in LV of SH rats. These findings suggest that encapsulation of CAR in NMs improved its ability to control central hemodynamics in SH rats when compared with CAR-LCF, mainly due to a greater effect on carotid systolic BP and short-term BP variability, resulting in a higher protection against TOD compared to CAR-LCF.