Design, optimization, characterization and in-vivo evaluation of Quercetin enveloped Soluplus®/P407 micelles in diabetes treatment

Abstract

Quercetin (Qu), is a flavonoid known to have anti-diabetic effects owing to its antioxidant property, thus promoting regeneration of the pancreatic islets, ultimately increasing insulin secretion. But the therapeutic application of Qu is hampered by its low oral bioavailability and its unfavourable physicochemical characteristics. The present work aimed at formulation of Quercetin loaded SoluplusV R micelles (SMs) so as to enhance its bioavailability and provide prolonged release for the management of diabetes. Box-Behnken response surface methodology was employed to optimize the formulation prepared using co-solvent evaporation method. Physicochemical characterization confirmed the nanospherical nature of Quercetin loaded SoluplusV R micelles (Qu-SMs) with average particle size ranging from 85-108nm, encapsulation efficiency of 63-77%. Solid state characterization confirmed the encapsulation of Qu in the micelles without any incompatibilities. Moving forward, the results of in vitro study revealed prolonged and slow release of Qu from the developed formulations. The in vivo pharmacokinetic study revealed improved bioavailability by enveloping the drug in SMs. Moreover, the study performed to evaluate the efficiency in diabetes treatment revealed an enhanced anti-diabetic effect. Thus, Qu-SMs can serve as potential carriers aimed at improving the anti-diabetic property of Qu.

Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy

“…Oral delivery of quercetin-succinylated chitosan-alginate core-shell-corona structured nanoparticles remarkably improved oral hypoglycaemic effect of quercetin in diabetic rats compared to native oral quercetin [224]. Quercetin-loaded Soluplus micelles have been found to improve the oral bioavailability (> 16%) of quercetin and maintained a prolonged release pattern in the management of diabetes in rats [225]. Oral delivery of quercetin-conjugated superparamagnetic iron oxide nanoparticles has been found to ameliorate diabetes-provoked memory impairment in rats at a much lower dose compared to free quercetin [226].…”

Comparison of Chitosan Nanoparticles and Soluplus Micelles to Optimize the Bioactivity of Posidonia oceanica Extract on Human Neuroblastoma Cell Migration

“…Soluplus/P407 release a 6.8% of quercetin in the first 8 h and a 28.75% after 24 h [44]. Evidence of a prolonged lag time in POE release encourages the use of polymeric micelles to optimize POE release.…”

“…This ability might be attributed to the interactions between the drug and the polymer. For example, the phenolic groups might interact with the terminal −OH and ether oxygen groups in Soluplus and form hydrogen bonds [44]. In the case of NP-POE, the encapsulation efficiency was calculated by the indirect method [33], as reported in the experimental section, because the direct method employs drastic conditions [38] which can alter the stability of the extract.…”

“…This ability might be attributed to the interactions between the drug and the polymer. For example, the phenolic groups might interact with the terminal −OH and ether oxygen groups in Soluplus and form hydrogen bonds [44]. The morphological characterization of PM-POE is reported in Figure 2B.…”

“…The release of the extract from PM-POE is not immediate but rather delayed, it begins to increase after 5 h, reaching 40% after 8 h, 50% after 12 h, and 90% after 72 h. The obtained results are in agreement with the literature, which refers to a time-delayed release by PM formulations. In fact, it was recently observed that polymeric micelles of Soluplus/P407 release a 6.8% of quercetin in the first 8 h and a 28.75% after 24 h [44]. Evidence of a prolonged lag time in POE release encourages the use of polymeric micelles to optimize POE release.…”