Mona Ebrahim

Hesperidin (Hsd), a promising bioactive phytomedicine, possesses a wound-healing activity. However, its poor solubility necessitates frequent topical application of high doses. Hence, this study aimed to prepare and characterize Hsd-loaded hybrid nanoparticles (Hsd-HNPs), followed by surface coating with chitosan (CS) to overcome such obstacles. Hsd was first encapsulated in a poly (D, L-lactic-co-glycolic) acid/soy phosphatidylcholine (PLGA/SPC) matrix, producing Hsd-HNPs, which were evaluated to choose the most appropriate one (F2). Then, F2 was coated with three concentrations of CS, and F2/CS 1 was the optimal one, with a homogenous particle size of 254.10 ± 4.59 nm, a positive zeta potential of 24.23 ± 2.70 mV, a percent Hsd entrapping efficiency of 60.41 ± 4.56 %, and a percent yield of 75.67 ± 2.36 %. The stability of F2/CS 1 was studied at a refrigerated temperature of 4 ± 1 • C. Then, it was incorporated into a gel base and subjected to further investigation of ex vivo skin permeation and in vivo wound healing activity. F2/CS 1 demonstrated good stability at 4 ± 1 • C. The results of permeation studies manifested an enhanced pattern of Hsd permeation from F2/CS 1 gel compared to that of the free Hsd. After topical application of F2/CS 1 gel to the induced wound rat model, a significant and prominent wound healing efficacy was emphasized by histopathological and immunohistochemical examinations. In conclusion, Hsd/CS-HNPs (F2/CS 1) gel could be regarded as promising topical nanophytomedicine with enhanced permeation and potentiated wound healing activity.

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-βcyclodextrin/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.