Saudi Journal of Biological Sciences 2020-Jan
Poloxamer-chitosan-based Naringenin nanoformulation used in brain targeting for the treatment of cerebral ischemia.
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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.