Enhancement of oral bioavailability of quercetin by metabolic inhibitory nanosuspensions compared to conventional nanosuspensions

Abstract

Quercetin-loaded nanosuspensions (Que-NSps) added metabolic inhibitors were evaluated as drug delivery system to promote the oral bioavailability of quercetin. Que-NSps were prepared respectively using D-alpha tocopherol acid polyethylene glycol succinate (TPGS) or Soybean Lecithin (SPC) as stabilizer. On the basis, Piperine (Pip) or sodium oleate (SO) was, respectively, encapsulated in Que-NSps as phase II metabolic inhibitors. The resulting Que-NSps all displayed a mean particle size of about 200 nm and drug loading content was in the range of 22.3-27.8%. The release of quercetin from Que-NSps was slow and sustained. After oral administration of 50 mg/kg different Que-NSps, the levels of free quercetin in plasma were significantly promoted, the concentration of quercetin metabolites (isorhamnetin and quercetin 3-O-b-D-Glucuronide) were decreased. The absolute bioavailability was, respectively 15.55%, 6.93%, 12.38%, and 23.58% for TPGS-Que-NSps, TPGS-SO-Que-NSps, SPC-Que-NSps, and SPC-Pip-Que-NSps, and 3.61% for quercetin water suspension. SPC-Pip-Que-NSps turned out to an ideal nanocarrier combined nano drug delivery system together with metabolic inhibitor to promote oral absorption of quercetin.

Quercetin Ameliorates Testicular Damage in Zucker Diabetic Fatty Rats through Its Antioxidant, Anti-Inflammatory and Anti-Apoptotic Properties

“…While the biomolecule is able to easily enter the cells through the phospholipid bilayer [70], it has poor aqueous solubility and is instable in physiological media [69]. As such, its absorption in the digestive tract is reduced since the intestinal cells are surrounded by a mucus layer with 90% water content [71]. If the mucus barrier is trespassed, QUE is rapidly metabolized in the liver and blood via glucuronidation, methylation, and sulfation [72], which is why glucuronic acid, sulfate, or methyl conjugates are found in blood as opposed to QUE aglycone [73].…”

“…This opens the question of whether metabolites derived from QUE would be more suitable for therapeutic intervention; nevertheless, it has been revealed that the in vivo activity major QUE-derived metabolites such as QUE glucosides are much weaker than QUE itself [74] or QUE aglycone. As such, scientific effort has switched towards novel vehicles to improve oral absorption and bioavailability of QUE, out of which micelles, liposomes, and nanosuspensions show promising preliminary results [69,71]. In this study, we elected a more conservative approach to administer QUE via biscuits, which are conveniently prepared without the necessity for sophisticated equipment.…”

Natural Kinase Inhibitors for the Treatment and Management of Endometrial/Uterine Cancer: Preclinical to Clinical Studies

“…Pharmacologically, nanoparticles showed multifunctional effects via inhibition of Aβ aggregation, destabilizing Aβ fibrils, decreasing Aβ-induced oxidative stress and Aβ-mediated cytotoxicity, and opening new channels for the treatment of amyloid-related diseases. Another group of researchers increased the bioavailability of quercitin via preparing nanosuspensions consisting of stabilizers such as d-alpha-tocopherol acid polyethylene glycol succinate (TPGS)/soybean lecithin and metabolism inhibitors, i.e., piperine and sodium oleate ( Li H. et al, 2021 ). The presence of stabilizers and metabolism inhibitors increased the oral bioavailability as evident by in vivo studies in animal models in comparison to traditional nanosuspensions.…”

Chemometric-Assisted UV-Spectrophotometric Method for Quantification of Novel Anti-Tubercular Liquisolid Formulation

“…It displays aversion to extremist searching, oxidants and restraint toward atherosclerotic activities. Quercetin has appeared to build bioavailability, blood levels and adequacy of various medications, including diltiazem, digoxin, verapamil, etoposide, and paclitaxel [13][14][15]. According to the literature, numerous methods, including UV spectroscopy [16,17], RP-HPLC [18][19][20], HPTLC [21,22] and others, are available for determining RIF both alone and in conjunction with various drugs in a variety of dose forms.…”