A novel therapeutic application of solid lipid nanoparticles encapsulated thymoquinone (TQ-SLNs) on 3-nitroproponic acid induced Huntington’s disease-like symptoms in wistar rats

• Targeted drug delivery system against 3-NP induced HD has been developed.
• 3-NP causes behavioral deficits via striatal lesions and oxidative stress.
• TQ-SLNs treatment restored the behavioral despairs and oxidative injury than TQ-S.
• TQ-SLNs also protected the striatal structural microelements from 3-NP toxicity.
• Study signifies TQ-SLNs a potent neuroprotective formulation upon 3-NP induction.

Huntington’s disease (HD), a devastating neurodegenerative disease causing a remarkable pathogenesis involves mitochondrial dysfunction and bioenergetics failure. 3-Nitropropionic acid (3-NP) is a unique toxin model of HD that are mainly confined to mitochondrial complex-II inhibition and free radical generation. Recently, several nanoparticle formulations were developed to treat against various neurodegenerative diseases including HD. One among them is solid lipid nanoparticles (SLNs), a colloidal carrier designed to enhance the brain drug delivery and to prolong the bio-availability of drugs in the system. Hence, the present study was framed to evaluate solid lipid nanoparticles encapsulated thymoquinone (TQ-SLNs) in comparison with thymoquinone suspension (TQ-S) against 3-NP induced behavioral despair, oxidative injury and striatal pathology. This study reports that theTQ-SLNs (10 and 20 mg/kg) and TQ-S (80 mg/kg) treated animals showed a significant (P < 0.01) improvement in the muscle strength, rigidity, movement and memory performances on 7th and 14th day behavioral analysis than TQ-S (40 mg/kg) treated group. Similarly, TQ-SLNs highly attenuated the levels of oxidative stress markers such as LPO, NO and protein carbonylsin 3-NP induced animals. Further, TQ-SLNs significantly restored the antioxidant defense system, controls the mitochondrial SDH inhibition and alleviates anti-cholinergic effect upon 3-NP induction. In addition, TQ-SLNs efficiently protected the striatal structural microelements against 3-NP toxicity, which was confirmed by light microscopic studies. Thus, the present investigation, collectively suggests that the low dose of TQ-SLNs supplementation is highly sufficient to attain the effect of TQ-S (80 mg/kg) to attenuate behavioral, biochemical and histological modifications in 3-NP exposed HD model.