Formulation and evaluation of nano lipid formulation containing CNS acting drug: molecular docking, in-vitro assessment and bioactivity detail in rats

Abstract

The study performed molecular docking, formulated, characterized thymoquinone (TQ) loaded solid lipid nano particles (TQSLN) and exhibited comparative antidepressant activity. TQ loaded nano lipid formulations were prepared by solvent injection methods and characterize for different in-vitro parameters. The optimized formulation was evaluated for depression using unpredictable chronic mild stress (UCMS) model for a period of six weeks. TQSLN was assessed in modified forced swim test (MFST), tail suspension test (TST), locomotor activity followed by biochemical parameters such as monoaminesand brain derived neurotrophic factor (BDNF). The results of molecular docking study revealed that TQ has shown greater affinity and tighter binding capacity for the active site of neurotransmitter receptors. TQSLN showed nanometric size, optimum zeta potential with high percent encapsulation and lower poly dispersity index (PDI). Transmission electron microscopy (TEM) images showed spherical shape without aggregation and agglomeration of particles. The in-vivo study result revealed that the higher amount of TQ reaches to the target region by showing higher levels of monoamines 5 hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) as compared to thymoquinone suspension (TQS) in brain. In conclusion, the nano lipid formulation remarkably improved the bio-efficacy of TQ and demonstrated a promising perspective for oral delivery of poorly water-soluble drugs.