Thymoquinone-Enriched Naringenin-Loaded Nanostructured Lipid Carrier for Brain Delivery via Nasal Route: In Vitro Prospect and In Vivo Therapeutic Efficacy for the Treatment of Depression

In the current research, a thymoquinone-enriched naringenin (NGN)-loaded nanostructured lipid carrier (NLC) was developed and delivered via the nasal route for depression. Thymoquinone (TQ) oil was used as the liquid lipid and provided synergistic effects. A TQ- and NGN-enriched NLC was developed via the ultrasonication technique and optimized using a central composite rotatable design (CCRD).

The optimized NLC exhibited the following properties: droplet size, 84.17 to 86.71 nm; PDI, 0.258 to 0.271; zeta potential, −8.15 to −8.21 mV; and % EE, 87.58 to 88.21%. The in vitro drug release profile showed the supremacy of the TQ-NGN-NLC in comparison to the NGN suspension, with a cumulative drug release of 82.42 ± 1.88% from the NLC and 38.20 ± 0.82% from the drug suspension. Ex vivo permeation study displayed a 2.21-fold increase in nasal permeation of NGN from the NLC compared to the NGN suspension. DPPH study showed the better antioxidant potential of the TQ-NGN-NLC in comparison to NGN alone due to the synergistic effect of NGN and TQ oil.

CLSM images revealed deeper permeation of the NGN-NLC (39.9 µm) through the nasal mucosa in comparison to the NGN suspension (20 µm). Pharmacodynamic studies, such as the forced swim test and the locomotor activity test, were assessed in the depressed rat model, which revealed the remarkable antidepressant effect of the TQ-NGN-NLC in comparison to the NGN suspension and the marketed formulation. The results signify the potential of the TQ-enriched NGN-NLC in enhancing brain delivery and the therapeutic effect of NGN for depression treatment.

Download the full article as a PDF here or read it here

Materials: Naringenin and TQ oil were purchased as gift samples from Sigma-Aldrich Co. (Spruce St Saint Louis, MO, USA). Gelucire 39/01, glyceryl monostearate, Compritol, Precirol ATO-5, Labrafil M 2130 CS, and Cremophor-EL were purchased from Gattefosse India Pvt. Ltd (Mumbai, India). Ascorbic acid and Rhodamine B were purchased from Sigma-Aldrich (Mumbai, India). Methanol and ethanol were obtained from Merck (Mumbai, India). 1,1-Diphenyl-2-picrylhydrazyl and 5,5′-dithiobis-2-nitrobenzoic acid were purchased from Sigma-Aldrich Chemicals Pvt. Ltd. (Bangalore, Karnataka, India). Sefsol® 218 was purchased from S D Fine Chem Limited (Mumbai, India). All other purchased solvents and chemicals were of analytical grade.

Article information: Qizilbash, F.F.; Ashhar, M.U.; Zafar, A.; Qamar, Z.; Annu; Ali, J.; Baboota, S.; Ghoneim, M.M.; Alshehri, S.; Ali, A. Thymoquinone-Enriched Naringenin-Loaded Nanostructured Lipid Carrier for Brain Delivery via Nasal Route: In Vitro Prospect and In Vivo Therapeutic Efficacy for the Treatment of Depression. Pharmaceutics 2022, 14, 656. https://doi.org/10.3390/pharmaceutics14030656