The Anti-Arthritic Efficacy of Khellin Loaded in Ascorbyl Decanoate Nanovesicles after an Intra-Articular Administration

Vanti, Giulia; Mannelli, Lorenzo Di Cesare; Micheli, Laura; Cinci, Lorenzo; Grifoni, Lucia; Bergonzi, Maria Camilla; Ghelardini, Carla; Bilia, Anna Rita

doi:10.3390/pharmaceutics13081275

Cited by 8 publications

(6 citation statements)

References 34 publications

(39 reference statements)

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“…Quantitative analyses of khellin were carried out using an 1100 High-Performance Liquid Chromatograph (HPLC) equipped with a Diode Array Detector (DAD) (Agilent Technologies Italia Spa; Rome, Italy), and an Eclipse XDB-C18 column with an internal diameter of 3.5 µm and (150 × 4.6) mm dimensions [37]. All the analyses were performed using a gradient analytical method with a flow rate of 0.4 mL/min and a mobile phase composed of (A) formic acid/water (pH 3.2), (B) acetonitrile.…”

Section: Quantitative Analysis By High Performance Liquid Chromatographymentioning

confidence: 99%

Nanostructured Lipid Carriers Can Enhance Oral Absorption of Khellin, a Natural Pleiotropic Molecule

et al. 2021

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A novel formulation based on nanostructured lipid carriers (NLCs) was developed to increase solubility and intestinal absorption of khellin. K-NLCs were prepared with stearic acid, hempseed oil, Brij S20, and Labrafil M 1944 CS, using the emulsification-ultrasonication method. Developed nanoparticles were chemically and physically characterized by liquid chromatography, light scattering techniques, and electron microscopy. The size, about 200 nm, was optimal for oral delivery, and the polydispersity index (around 0.26), indicated high sample homogeneity. Additionally, K-NLCs showed a spherical morphology without aggregation by microscopic analysis. The encapsulation efficiency of khellin was about 55%. In vitro release studies were carried out in media with different pH to mimic physiological conditions. K-NLCs were found to be physically stable in the simulated gastric and intestinal fluids, and they preserved about 70% of khellin after 6 h incubation. K-NLCs were also successfully lyophilized testing different lyoprotectants, and obtained freeze-dried K-NLCs demonstrated good shelf life over a month. Lastly, permeability studies on Caco-2 cells were performed to predict khellin passive diffusion across the intestinal epithelium, demonstrating that nanoparticles increased khellin permeability by more than two orders of magnitude. Accordingly, developed NLCs loaded with khellin represent a versatile formulation with good biopharmaceutical properties for oral administration, possibly enhancing khellin’s bioavailability and therapeutic effects.

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Section: Quantitative Analysis By High Performance Liquid Chromatographymentioning

confidence: 99%

Nanostructured Lipid Carriers Can Enhance Oral Absorption of Khellin, a Natural Pleiotropic Molecule

et al. 2021

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“…These figures were similar due to the high affinity of khellin towards the lipophilic environment of the stratum corneum forming momentous depots because of the low value of octanol/water partition coefficient (ca. 3), the melting point (154 – 155 °C) and molecular weight (260.24 Da) 15 , 16 , 17 .…”

Section: Resultsmentioning

confidence: 99%

“…The in vitro drug diffusion and release kinetics were carried out using Franz cells; the system consists of two chambers, donor and acceptor, separated by a horizontally oriented membrane according to a previous study [17]. Cellulose nitrate filters (Sartorius Stedim Biotech GmbH, Germany), with 0.45 µm pore sizes and 130 µm thickness, were used.…”

Section: In Vitro Drug Diffusion and Release Kineticsmentioning

confidence: 99%

Development and Evaluation of Khellin-loaded Microemulgel for Dermatological Applications

et al. 2022

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Microemulsions are optically nanosized emulsions, isotropic and thermodynamically stable. They represent versatile drug delivery systems with high potential because can be administered through all routes. In the present study, we report on the formulation of a microemulsion made with glycerol (2.25%), Labrasol (20.25%) vitamin E acetate (2.50%), and water (75.00%), which was developed using the pseudo-ternary phase diagram. Globules of the microemulsion had PdI less than 0.25 and size of about 17 nm, evaluated by DLS analysis. These values did not change after loading khellin, a natural lipophilic molecules with interesting biological activities, used as a model of lipophilic drug. Carboxymethyl cellulose was selected as gelling polymer to obtain a microemulgel. Viscosity was 22,100.0±1555.6 mPas·s at 21±2°C, while it was 8,916.5±118.1 mPas·s at 35±2°C, remaining stable over time. Khellin recovery was 93.16±4.39% and it was unchanged after 4 weeks of storage (93.23±2.14%). The pH was 6.59±0.19 and it was found 6.42±0.34 at the end of the storage lifetime. The diffusion of khellin from the developed formulation was prolonged over an extended period. Based on overall results and due to the dermatological properties of the ingredients of the formulation, the developed microemulgel loaded with khellin is very promising and suitable for skin care applications.

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“…Neurological function and balance capacity were assessed using a modification of the Longa mothed ( Longa et al, 1989 ) and the balance beam test ( Vanti et al, 2021 ), respectively. The standards of neurological function score and beam balance test are listed in Supplementary Tables S2,S3 .…”

Section: Methodsmentioning

confidence: 99%

Integrated Analysis of the Cecal Microbiome and Plasma Metabolomics to Explore NaoMaiTong and Its Potential Role in Changing the Intestinal Flora and Their Metabolites in Ischemic Stroke

et al. 2022

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Ischemic stroke (IS), as a leading cause of disability worldwide, affects intestinal bacterial communities and their metabolites, while recent discoveries have highlighted the importance of the intestinal microflora in the development of IS. Systematic investigations of complex intestinal bacterial communities and their metabolites during ischemic brain injury contribute to elucidate the promising therapeutic targets for IS. However, the associations between intestinal microbiota and related circulating metabolic processes in IS remained unclear. Hence, to identify the changed microflora and their metabolites in IS of NaoMaiTong (NMT), an effective clinical medication, we established the middle cerebral artery occlusion/reperfusion (MCAO/R) model using conventionalized and pseudo-germ-free (PGF) rats. Subsequently, we systematically screen the microflora and related metabolites changing in IS via an integrated approach of cecal 16S rRNA sequencing combined with plasma metabolomics. We found that NMT relied on intestinal flora to improve stroke outcome in conventionalized rats while the protection of NMT was reduced in PGF rats. Total 35 differential bacterial genera and 26 differential microbial metabolites were regulated by NMT. Furthermore, L-asparagine and indoleacetaldehyde were significantly negatively correlated with Lachnospiraceae_UCG.001 and significantly positively correlated with Lachnoclostridium. Indoleacetaldehyde also presented a negative correlation with Lactobacillus and Bifidobacterium. 2-Hydroxybutyric acid was strongly negatively correlated with Ruminococcus, Lachnospiraceae_UCG.001 and Lachnospiraceae_UCG.006. Creatinine was strongly negatively correlated with Akkermansia. In summary, the research provided insights into the intricate interaction between intestinal microbiota and metabolism of NMT in IS. We identified above differential bacteria and differential endogenous metabolites which could be as prebiotic and probiotic substances that can influence prognosis in stroke and have potential to be used as novel therapeutic targets or exogenous drug supplements.

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The Anti-Arthritic Efficacy of Khellin Loaded in Ascorbyl Decanoate Nanovesicles after an Intra-Articular Administration

Cited by 8 publications

References 34 publications

Nanostructured Lipid Carriers Can Enhance Oral Absorption of Khellin, a Natural Pleiotropic Molecule

Nanostructured Lipid Carriers Can Enhance Oral Absorption of Khellin, a Natural Pleiotropic Molecule

Development and Evaluation of Khellin-loaded Microemulgel for Dermatological Applications

Integrated Analysis of the Cecal Microbiome and Plasma Metabolomics to Explore NaoMaiTong and Its Potential Role in Changing the Intestinal Flora and Their Metabolites in Ischemic Stroke

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