Self-Nanoemulsifying Drug Delivery System Loaded with Psiadia punctulata Major Metabolites for Hypertensive Emergencies: Effect on Hemodynamics and Cardiac Conductance

Abstract

Vasodilators are an important class of antihypertensive agents. However, they have limited clinical use due to the reflex tachycardia associated with their use which masks most of its antihypertensive effect and raises cardiac risk. Chemical investigation of Psiadia punctulata afforded five major methoxylated flavonoids (1–5) three of which (1, 4, and 5) showed vasodilator activity. Linoleic acid-based self-nanoemulsifying drug delivery system (SNEDDS) was utilized to develop intravenous (IV) formulations that contain compounds 1, 4, or 5. The antihypertensive effect of the prepared SNEDDS formulations, loaded with each of the vasodilator compounds, was tested in the angiotensin-induced rat model of hypertension. Rats were subjected to real-time recording of blood hemodynamics and surface Electrocardiogram (ECG) while the pharmaceutical formulations were individually slowly injected in cumulative doses. Among the tested formulations, only that contains umuhengerin (1) and 5,3′-dihydroxy-6,7,4′,5′-tetramethoxyflavone (5) showed potent antihypertensive effects. Low IV doses, from the prepared SNEDDS, containing either compound 1 or 5 showed a marked reduction in the elevated systolic blood pressure by 10 mmHg at 12 μg/kg and by more than 20 mmHg at 36 μg/kg. The developed SNEDDS formulation containing either compound 1 or 5 significantly reduced the elevated diastolic, pulse pressure, dicrotic notch pressure, and the systolic–dicrotic notch pressure difference. Moreover, both formulations decreased the ejection duration and increased the non-ejection duration while they did not affect the time to peak. Both formulations did not affect the AV conduction as appear from the lack of effect on p duration and PR intervals. Similarly, they did not affect the ventricular repolarization as no effect on QTc or JT interval. Both formulations decreased the R wave amplitude but increased the T wave amplitude. In conclusion, the careful selection of linoleic acid for the development of SNEDDS formulation rescues the vasodilating effect of P. punctulata compounds from being masked by the reflex tachycardia that is commonly associated with the decrease in peripheral resistance by most vasodilators. The prepared SNEDDS formulation could be suggested as an effective medication in the treatment of hypertensive emergencies, after clinical evaluation.

Phenolics from Chrozophora oblongifolia Aerial Parts as Inhibitors of α-Glucosidases and Advanced Glycation End Products: In-Vitro Assessment, Molecular Docking and Dynamics Studies

“…The genus is characterized by the presence of phenolic compounds [14] that showed different biological activities including anti-microbial [15], α-glucosidase inhibitory [16], anti-inflammatory [17], and osteoprotective [18]. In continuation of our work on diabetic complications [4,[19][20][21] and based on the few data concerning active constituents of C. oblongifolia (L.) A. Juss; it was deemed important to carry out a biological investigation of its phenolic constituents and assess their effect on diabetic complications.…”

Development of 3D-Printed, Liquisolid and Directly Compressed Glimepiride Tablets, Loaded with Black Seed Oil Self-Nanoemulsifying Drug Delivery System: In Vitro and In Vivo Characterization

“…Additionally, SNEDDS offer a good alternative to the conventional oral formulations of lipophilic compounds [23]. Previously published works indicated the good stability and small globule size of SNEDDS prepared utilizing tween 80 and PEG 400 with different oils such as sefsol, linoleic acid, olive oil, oleic acid and isopropyl myristate [25].…”

Hinokitiol for hypertensive emergencies: Effects on peripheral resistance, cardiac load, baroreflex sensitivity, and electrolytes balance

“…The i.v. hinokitiol formulation was prepared as previously described in our previous study [17]. In brief, 24 mg of hinokitiol was added to 1 gram of self-nanoemulsifying drug delivery system (SNEDDS) formulation which contains 10% linoleic acid, 80% polyethylene glycol 400, and 10% tween 80.…”

“…"n" values refer to independent animals and not replicates. The sample size and animal numbers were determined by power analysis of pre-existing data [17,21]. The studies were designed to generate groups of equal size, using randomisation and blinded analysis.…”