Design and optimization of myricetin encapsulated nanostructured lipid carriers: In-vivo assessment against cognitive impairment in amyloid beta (1–42) intoxicated rats

Abstract

Aims: This research aimed to evaluate the potential of MY loaded nanostructured lipid carrier (MY-NLCs) to ameliorate the bioavailability in the brain and cognitive impairment in Aβ induced Alzheimer’'s model. Materials and Methods: MY-NLCs were prepared with precirol ATO 5, labrafac lipophile WL 1349, and tween 80 as solid lipid, liquid lipid, and surfactant respectively. The formulation was optimized with central composite design (CCD) and characterized by different parameters. Cellular toxicity and uptake studies were evaluated in SH-SY5Y cells. MY concentration in plasma and brain was analyzed after the i.p. administration of MYS and MYNLCs (40 mg/kg) in Sprague–Dawley rats (n = 3). Further, the pharmacodynamic studies were evaluated in the (Aβ1-–42) induced (5 μg/5 μl, ICV, unilateral) Alzheimer’'s rat model (n = 6) and cognitive performance was assessed using Morris water maze test followed by histological and neurotransmitters analyses in rats’' brain. Key findings: The optimized MY-NLCs exhibited 89.7 ± 26.0 nm particle size, 80.81 ± 10.39% entrapment efficiency, and 5.08 ± 1.0% of drug loading capacity. The in-vitro release studies revealed a biphasic release pattern and also demonstrated distinct cellular internalization in SH-SY5Y cells. MY-NLCs exhibited 2.77 folds higher AUC 0–24 in plasma and drug targeting efficiency for MY into the brain was found 127.05% as compared to MYS. The mitigating potential of MY-NLCs (10 mg/kg) was also significantly observed in behavioral parameters and in the regulation of neurotransmitters levels in rat brain. Significance: MY-NLCs would be explored as an alternative promising drug delivery platform for several neurodegenerative payloads.