Plausible antioxidant biomechanics and anticonvulsant pharmacological activity of brain-targeted β-carotene nanoparticles

Abstract

β-Carotene has been established as a known free radical scavenger with chainbreaking antioxidant properties. It has been documented for the treatment of epileptic convulsions at a 200 mg/kg body weight dose. The reported pathogenesis for epileptic convulsions is oxidative stress. Hence, experimental epileptic convulsions via oxidative stress was induced in albino mice epileptic models (maximal electroshock seizure and pentylenetetrazole [PTZ]). A dose concentration equivalent to 2 mg/kg was efficaciously administered in the form of brain-targeted polysorbate-80-coated poly(d,l-lactide-co-glycolide) nanoparticles. The nanoparticles were prepared by solvent evaporation technique and further characterized for their physical parameters, in-vitro release kinetics, and in-vivo brain release via various standard methods. Normal β-carotene nanoparticles (BCNP) and polysorbate-80-coated β-carotene nanoparticles (P-80-BCNP) of 169.8 ± 4.8 nm and 176.3 ± 3.2 nm in size, respectively, were formulated and characterized. Their zeta potential and polydispersity index were subsequently evaluated after 5 months of storage to confirm stability. In vivo activity results showed that a 2 mg unformulated β-carotene dose was ineffective as an anticonvulsant. However, salutary response was reported from BCNP at the same dose, as the hind limb duration decreased significantly in maximal electroshock seizure to 9.30 ± 0.86 seconds, which further decreased with polysorbate-80 coating to 2.10 ± 1.16 seconds as compared to normal control (15.8 ± 1.49 seconds) and placebo control (16.50 ± 1.43 seconds). In the PTZ model, the duration of general tonic-clonic seizures reduced significantly to 2.90 ± 0.98 seconds by the use of BCNP and was further reduced on P-80-BCNP to 1.20 ± 0.20 seconds as compared to PTZ control and PTZ-placebo control (8.09 ± 0.26 seconds). General tonic-clonic seizures latency was increased significantly to 191.0 ± 9.80 seconds in BCNP and was further increased in P-80-BCNP to 231.0 ± 16.30 seconds, as compared to PTZ (120.10 ± 4.50 seconds) and placebo control (120.30 ± 7.4 seconds). The results of this study demonstrate a plausible novel anticonvulsant activity of β-carotene at a low dose of 2 mg/kg, with brain-targeted nanodelivery, thus increasing its bioavailability and stability.

Bio-Based Nanoparticles as a Carrier of β-Carotene: Production, Characterisation and In Vitro Gastrointestinal Digestion

“…Results show that a higher amount of antisolvent resulted in higher PDI, varying from 0.29 to 0.20, at 0.7 mL/min flow rate and 0.4% zein concentration. PDI measures the homogeneity of the NPs dispersion, PDI values greater than 0.5 can represent aggregation of particles [ 41 ] but for the tested conditions all measurements stayed below this value.…”

Nanotechnology inspired tools for mitochondrial dysfunction related diseases

“…β-Carotene is an antioxidant known for its epileptic convulsions. Bioavailability and stability of polysorbate-80-coated β-carotene nanoparticles for epileptic convulsions in mice models was found to be higher when compared to unmodified β-carotene (49). …”

“…DQA was also used with TPGS1000, known as vitamin E polyethylene glycol succinate, to construct mitochondria targeting liposomes for the delivery of chemotherapeutic drug, topotecan hydrochloride a topoisomerase I inhibitor. These mitochondria targeted topotecan entrapped liposomes demonstrated higher efficacy for treatment of chemo-resistant cancer and showed inhibition of metastases in vivo (49). …”

Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs

“…Solid lipid nanoparticles loaded with carbamazepine (Samia et al, 2012) and PLGA nanoparticles loaded with β-carotene (Yusuf et al, 2012) have been found to show more potential for anticonvulsant effect than nanoemulged loaded carbamazepine and polysorbate-80 coated PLGA nanoparticles, respectively. In a rat model, liposomal muscimol formulation (Kohane et al, 2002) has been reported to suppress focal seizures while producing minimal histological alterations, and amiloride loaded liposomes (Ali et al, 2007) demonstrated higher anticonvulsant potential in comparison to the free drug in a mice model.…”