Enhanced oral delivery of hesperidin-loaded sulfobutylether-β-cyclodextrin/chitosan nanoparticles for augmenting its hypoglycemic activity: in vitro-in vivo assessment study

Abstract

Hesperidin (Hsd), a bioactive phytomedicine, experienced an antidiabetic activity versus both Type 1 and Type 2 Diabetes mellitus. However, its intrinsic poor solubility and bioavailability is a key challenging obstacle reflecting its oral delivery. From such perspective, the purpose of the current study was to prepare and evaluate Hsd-loaded sulfobutylether-β-cyclodextrin/chitosan nanoparticles (Hsd/CD/CS NPs) for improving the hypoglycemic activity of the orally administered Hsd. Hsd was first complexed with sulfobutylether-β-cyclodextrin (SBE-β-CD) and the complex (CX) was found to be formed with percent complexation efficiency and percent process efficiency of 50.53 ± 1.46 and 84.52 ± 3.16%, respectively. Also, solid state characterization of the complex ensured the inclusion of Hsd inside the cavity of SBE-β-CD. Then, Hsd/CD/CS NPs were prepared using the ionic gelation technique. The prepared NPs were fully characterized to select the most promising one (F1) with a homogenous particle size of 455.7 ± 9.04 nm, a positive zeta potential of + 32.28 ± 1.12 mV, and an entrapment efficiency of 77.46 ± 0.39%. The optimal formula (F1) was subjected to further investigation of in vitro release, ex vivo intestinal permeation, stability, cytotoxicity, and in vivo hypoglycemic activity. The results of the release and permeation studies of F1 manifested a modulated pattern between Hsd and CX. The preferential stability of F1 was observed at 4 ± 1 °C. Also, the biocompatibility of F1 with oral epithelial cell line (OEC) was retained up to a concentration of 100 µg/mL. After oral administration of F1, a noteworthy synergistic hypoglycemic effect was recorded with decreased blood glucose level until the end of the experiment. In conclusion, Hsd/CD/CS NPs could be regarded as a hopeful oral delivery system of Hsd with enhanced antidiabetic activity. Graphical Abstract

Network Pharmacology Analysis, Molecular Docking Integrated Experimental Verification Reveal the Mechanism of Gynostemma pentaphyllum in the Treatment of Type II Diabetes by Regulating the IRS1/PI3K/Akt Signaling Pathway

“…The results of molecular docking showed that nine active components had good binding ability with key protein INSR, including Ginkgolic acid (GA13:1), Ginkgolic acid (GA15:1), Gypenoside XXVII, Gypenoside XXVIII, Hesperetin, Nicotiflorin, Quercetin, Spinasterol and Gypenoside XVII. Recent studies show that hesperidin, quercetin and spinach sterol all have obvious therapeutic effects on diabetes [ 43 , 44 , 45 ], which further verifies the accuracy of screening active compounds by network pharmacology and molecular docking. In particular, we found that Gypenoside XVII could bind to six core proteins strongly, and the docking scores were high among the screened compounds.…”