Poloxamer-chitosan-based Naringenin nanoformulation used in brain targeting for the treatment of cerebral ischemia
| Autor: | Aftab Alam, Abuzer Ali, Mohd Amir, Farhan Jalees Ahmad, Wasim Ahmad, Niyaz Ahmad, Rizwan Ahmad |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
0301 basic medicine Naringenin Antioxidant medicine.medical_treatment MCAO-oxidative stress CS chitosan Pharmacology UHPLC-MS/MS-pharmacokinetic 01 natural sciences chemistry.chemical_compound TBARS thiobarbituric acid reactive substances lcsh:QH301-705.5 Q-TOF quadrupole time of flight Tmax time to Cmax MQC middle quality control ESI electrospray ionization TEM transmission electron microscope CLSM confocal laser scanning microscopy Cerebral ischemia LOD lower limit of detection NRG naringenin Kel elimination rate constant Toxicity BA bioavailability General Agricultural and Biological Sciences Quercetin LLOQ QC lower limit of quantification for quality control SEM scanning electron microscope Ischemia LLOQ lower limit of quantification AUC area under curve UHPLC-MS/MS ultra high performance liquid chromatography mass spectroscopy and mass spectroscopy PK pharmacokinetic Article Cmax maximum plasma concentration 03 medical and health sciences NE nanoemulsion Mucoadhesive-chitosan-based-nanoemulsion-gel medicine Potency MCAO middle cerebral artery occlusion ComputingMethodologies_COMPUTERGRAPHICS ANOVA. analysis of variance LOQ lower limit of quantitation PDI polydispersity index t½ half-life medicine.disease Bioavailability 030104 developmental biology LLE liquid–liquid extraction chemistry lcsh:Biology (General) HQC high quality control Nasal administration LQC low quality control 010606 plant biology & botany |
| Zdroj: | Saudi Journal of Biological Sciences, Vol 27, Iss 1, Pp 500-517 (2020) Saudi Journal of Biological Sciences |
| Popis: | Graphical abstract Objective Here, the aim is to improve the bioavailability of Naringenin (NRG) in brain and to establish the highest remedial benefit from a novel anti-ischemic medicine i.e. NRG. Methods A novel Naringenin-loaded-nanoemulsion (NE)-(in situ)-gel (i.e. thermoresponsive), was formulated with the help of Poloxamer-407 (20.0% w/v). Chitosan (CS, 0.50% w/v) was used to introduce the mucoadhesive property of NE-(in situ)-gel and finally called as NRG-NE-gel + 0.50%CS. A novel UHPLC-ESI-Q-TOF-MS/MS-method was optimized and used for NRG-NE-gel + 0.50%CS to quantify the Pharmacokinetic-(PK)-parameters in plasma as well as brain and to evaluate the cerebral ischemic parameters after MCAO i.e. locomotor activity, grip strength, antioxidant activity, and quantity the infarction volume in neurons with the safety/toxicity of NRG-NE-gel + 0.50%CS after i.n. administration in the rats. Results The mucoadhesive potency and gelling temperature of NRG-NE-gel + 0.50%CS were observed 6245.38 dynes/cm2 and 28.3 ± 1.0 °C, respectively. Poloxamer-407 based free micelles size was observed 98.31 ± 1.17 nm with PDI (0.386 ± 0.021). The pH and viscosity of NRG-NE-gel + 0.50%CS were found to be 6.0 ± 0.20 and 2447 ± 24cp (at 35.0 ± 1.0 °C temperature), respectively. An elution time and m/z NRG were observed 1.78 min and 270.97/150.96 with 1.22 min and m/z of 301.01/150.98 for Quercetin (IS) respectively. Inter and intra %precision and %accuracy was validated 1.01–3.37% and 95.10–99.30% with a linear dynamic range (1.00 to 2000.00 ng/ml). AUC0-24 of plasma & brain were observed 995.60 ± 24.59 and 5600.99 ± 144.92 (ng min/ml g) in the rats after the intranasal (i.n.) administration of NRG-NE-gel + 0.50%CS. No toxicological response were not found in terms of mortalities, any-change morphologically i.e. in the microstructure of brain as well as nasal mucosa tissues, and also not found any visual signs in terms of inflammatory or necrosis. Conclusion Intranasally administered NRG-NE-gel + 0.50%CS enhanced the bioavailability of Naringenin in the brain. In the cerebral ischemic rats, significantly improved the neurobehavioral activity (locomotor & grip strength) followed by antioxidant activity as well as infarction volume. Finally, the toxicity studies carried out and established the safe nature of optimized-NRG-NE-gel + 0.50%CS. |
| Databáze: | OpenAIRE |
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