Formulation of Apigenin-Cyclodextrin-Chitosan Ternary Complex: Physicochemical Characterization, In Vitro and In Vivo Studies

Jafar, Mohammed; Khalid, Mohammed Saifuddin; Alghamdi, Hajer Saleh; Amir, Mohd; Makki, Sarah Aon Al; Alotaibi, Ohud Saud; Rmais, Afnan Ali Al; Imam, Syed Sarim; Alshehri, Sultan; Gilani, Sadaf Jamal

doi:10.1208/s12249-022-02218-8

Cited by 9 publications

(6 citation statements)

References 51 publications

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“…This could be ascribed to intermolecular hydrogen bonding. Moreover, the complexation of Hsd was responsible for the reduction in its peak intensity which in turn contributes to the amorphousness of the CS NPs [ 132 , 133 ]. Such observation indicated that the presence of the complexed Hsd did not disturb the nanostructured architecture of the NPs [ 134 ].…”

Section: Resultsmentioning

confidence: 99%

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

Elmoghayer,

Saleh,

Abu Hashim

2023

Drug Deliv. and Transl. Res.

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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

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Section: Resultsmentioning

confidence: 99%

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

Elmoghayer,

Saleh,

Abu Hashim

2023

Drug Deliv. and Transl. Res.

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“…During drug development, the inclusion complex encapsulation ratio can be measured by a joint analytical approach, together with further studies, as reported for apigenin- HP-β-CD with -chitosan ternary complex formulation [ 36 ], including additional analysis, such as XRD evaluation and formulation dissolution. Here, the formation of the inclusion complex of psoralens and HP-β-CD were investigated by four different methods in solid state: Differential Scanning Calorimetry (DSC); Thermogravimetry (TG); Fourier transform infrared spectroscopy (FTIR), and Scanning electron microscopy (SEM), showing findings corroborating with the evidence of inclusion complex formation (see details on the following sections).…”

Section: Resultsmentioning

confidence: 99%

Improvement in Solubility–Permeability Interplay of Psoralens from Brosimum gaudichaudii Plant Extract upon Complexation with Hydroxypropyl-β-cyclodextrin

Machado

Silva

et al. 2022

Molecules

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Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Trécul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-β-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-β-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (Kc < 500 M−1). PSO and 5-MOP permeability rate decreased after adding HP-β-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-β-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-β-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo.

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“…Fortunately, in recent years, different delivery systems (liposomes, polymer micelles, and nanosuspensions) have helped improve the solubility and stability of poorly water-soluble drugs [ 15 ]. In particular, different API-loaded carriers have been developed to improve the solubility and bioactivity of API [ 20 , 51 , 52 ]. Next, to further explore the therapeutic efficacy of API, alternative routes of administration such as intraperitoneal injection or oral administration could be considered in our study.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of apigenin on retinal ganglion cells in ischemia/reperfusion: modulating mitochondrial dynamics in in vivo and in vitro models

Wu,

zhang,

Liu

et al. 2024

J Transl Med

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Background Retinal ischemia/reperfusion (RIR) is implicated in various forms of optic neuropathies, yet effective treatments are lacking. RIR leads to the death of retinal ganglion cells (RGCs) and subsequent vision loss, posing detrimental effects on both physical and mental health. Apigenin (API), derived from a wide range of sources, has been reported to exert protective effects against ischemia/reperfusion injuries in various organs, such as the brain, kidney, myocardium, and liver. In this study, we investigated the protective effect of API and its underlying mechanisms on RGC degeneration induced by retinal ischemia/reperfusion (RIR). Methods An in vivo model was induced by anterior chamber perfusion following intravitreal injection of API one day prior to the procedure. Meanwhile, an in vitro model was established through 1% oxygen and glucose deprivation. The neuroprotective effects of API were evaluated using H&E staining, spectral-domain optical coherence tomography (SD-OCT), Fluoro-Gold retrograde labeling, and Photopic negative response (PhNR). Furthermore, transmission electron microscopy (TEM) was employed to observe mitochondrial crista morphology and integrity. To elucidate the underlying mechanisms of API, the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, flow cytometry assay, western blot, cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay, JC-1 kit assay, dichlorofluorescein-diacetate (DCFH-DA) assay, as well as TMRE and Mito-tracker staining were conducted. Results API treatment protected retinal inner plexiform layer (IPL) and ganglion cell complex (GCC), and improved the function of retinal ganglion cells (RGCs). Additionally, API reduced RGC apoptosis and decreased lactate dehydrogenase (LDH) release by upregulating Bcl-2 and Bcl-xL expression, while downregulating Bax and cleaved caspase-3 expression. Furthermore, API increased mitochondrial membrane potential (MMP) and decreased extracellular reactive oxygen species (ROS) production. These effects were achieved by enhancing mitochondrial function, restoring mitochondrial cristae morphology and integrity, and regulating the expression of OPA1, MFN2, and DRP1, thereby regulating mitochondrial dynamics involving fusion and fission. Conclusion API protects RGCs against RIR injury by modulating mitochondrial dynamics, promoting mitochondrial fusion and fission.

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Formulation of Apigenin-Cyclodextrin-Chitosan Ternary Complex: Physicochemical Characterization, In Vitro and In Vivo Studies

Cited by 9 publications

References 51 publications

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

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

Improvement in Solubility–Permeability Interplay of Psoralens from Brosimum gaudichaudii Plant Extract upon Complexation with Hydroxypropyl-β-cyclodextrin

Neuroprotective effects of apigenin on retinal ganglion cells in ischemia/reperfusion: modulating mitochondrial dynamics in in vivo and in vitro models

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