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.

Lipid nanocarrier of selegiline augmented anti-Parkinson's effect via P-gp modulation using quercetin.

In the present study, SEL was loaded in a lipid nanocarrier (LNC) formulation with a P-gp pump inhibitor i.e., Quercetin (QUR) for improving the bioavailability of the SEL in the brain via the oral route. SEL-QUR LNC was formulated using modified emulsiosonication method and optimized using central composite rotatable design (CCRD) design. The results showed that optimized SEL-QUR LNC formulation was spherical with globule size, polydispersity index, entrapment efficiency and zeta potential within the range of 92.46-95.34 nm, 0.239-0.248, 88.94-91.26%, and -6.21 to -7.75 mV respectively. A 4-fold and 6-fold increase was observed in the permeation of SEL from SEL-QUR LNC across the gut sac in comparison with SEL-QUR and SEL suspensions respectively. CLSM images showed 2-fold deeper permeation of SEL across intestinal membrane demonstrating excellent in vivo prospect of the formulation. The behavioural studies including forced swimming, muscle coordination, locomotor activity, akinesia, and catalepsy were performed in the haloperidol-induced PD rats that demonstrated increased efficacy of the formulation in contrast to the SEL-QUR and SEL suspensions. These studies concluded that developed LNC formulation loaded SEL with P-gp inhibitor had the potential in improving bioavailability of SEL in the brain via oral route.

Role of Natural Bioactives and their Nanocarriers for Overcoming Oxidative Stress Induced Cancer.

BACKGROUND: Oxidative stress and free radicals are harmful to human health. Reactive oxygen species are the major source of oxidative stress and are one of the major causes of cancer development. Cancer is one of the leading causes of death worldwide. Prolonged use of synthetic chemotherapeutic due to their low bioavailability leads to systemic toxic side effects. To surmount this problem, the use of antioxidants is recommended as they have the ability to counteract oxidative stress and mitigate its effects on human health. They inhibit various pathways that are involved with the initiation and progression of cancer. Various nanoformulations have been used to deliver these antioxidants (curcumin, mangiferin, quercetin) in the treatment of various cancer for overcoming oxidative stress. OBJECTIVE: The main focus of this review article is to illustrate various studies performed using nanocarriers of natural bioactives to overcome oxidative stress and cancer associated with it. It also describes pathways associated with the induction, initiation and progression of cancer due to reactive oxidative species. METHODS: Research articles that focused on the use of natural bioactives and their nanoformulations for the treatment of various cancers induced due to oxidative stress, were collected from various search engines like PubMed, Science Direct and Google Scholar, using keywords like oxidative stress, antioxidants, cancers, ROS, etc. Conclusion: Natural bioactives have shown great potential in overcoming oxidative stress for the treatment of various cancers. However, extensive research is required so that these antioxidants and their nanocarriers can be used for the welfare of mankind, in the treatment of various cancers, in the near future.

CCRD based development of bromocriptine and glutathione nanoemulsion tailored ultrasonically for the combined anti-parkinson effect.

Bromocriptine Mesylate (BRM) acts as a dopamine receptor agonist along with antioxidant effect and is utilized in the treatment of Parkinson's disease (PD). Glutathione (GSH) is a thiol- reducing agent having antioxidant properties in the brain. Replenishment of GSH inside the brain can play a major role in the management of PD. Both BRM and GSH suffer from low oral bioavailability and poor absorption. The objective of the present study was to develop BRM and GSH loaded nanoemulsion for the combined and synergistic effect delivered through the intranasal route for the better and effective management of PD. After extensive screening experiments, Capmul PG-8 NF was selected as oil, polyethylene glycol (PEG) 400 as a surfactant and propylene glycol as co-surfactant. Ultrasonication technique was employed for the fabrication of nanoemulsion. Central composite rotatable design (CCRD) was used to obtain the best formulation by optimization. Oil (%), Smix (%), and sonication time (second) were chosen as independent variables for the optimization. Particle size, PDI, zeta potential, % transmittance, pH, refractive index, viscosity and conductivity of the optimized nanoemulsion were found to be 80.71 ± 2.75 nm, 0.217 ± 0.009, -12.60 ± 0.10 mV, 96.00 ± 3.05 %, 6.48 ± 0.28, 1.36 ± 0.03, 30.12 ± 0.10 mPas and 214.28 ± 2.79 µS/cm respectively. Surface morphology demonstrated that nanoemulsion possessed spherical and globular nature of the particle which showed 3.4 times and 1.5 times enhancement in drug permeation in the case of BRM and GSH respectively as compared to suspension. MTT assay done on neuro-2a cell lines revealed that nanoemulsion was safe for intranasal delivery. Behavioural studies were carried out to prove the efficacy of optimized nanoemulsion in PD using forced swimming test, locomotor activity test, catalepsy test, rota-rod test, and akinesia test in Wistar rats. The outcomes of the behavioural studies revealed that BRM and GSH loaded nanoemulsion treatment showed significant improvement in behavioural activities of PD (haloperidol-induced) rats after intranasal administration. This study concluded that BRM and GSH loaded nanoemulsion could be promising for the combined and synergistic anti-parkinson effect for the effective management of PD.

Intranasal pitavastatin attenuates seizures in different experimental models of epilepsy in mice.

This study was carried out to evaluate the effect of intranasal pitavastatin (PVS) on pentylenetetrazole (PTZ)-induced seizures, increasing current electroshock (ICES) seizures, and status epilepticus in mice. Intranasal PVS, 0.5 and 1.0mg/kg, showed significant increase in latency to PTZ-induced seizures and ICES seizure threshold compared to control; however, the effects were dose-dependent and were more significant at higher dose. Further, intranasal PVS (1.0mg/kg) but not intravenous PVS (50.0mg/kg) showed effective protection against PTZ-induced status epilepticus. No impairment in cognitive functions was observed following intranasal PVS (1.0mg/kg), thus making it a prospective therapeutic approach for acute seizures and status epilepticus.