Abstract
Background: Parkinsonism has a toxic cascade of neurodegeneration, with akinesia as a major manifestation. Some antioxidants have shown promise against the disease. Astaxanthin is a powerful antioxidant, demonstrates free radical scavenging, and is also a potential neuroprotective agent.
Objective: The objective of this study was to formulate astaxanthin-laden nanostructured lipid carriers based thermoreversible gel for better neuronal uptake and better neuronal efficacy.
Methods: The method for fabricating astaxanthin-nanostructured lipid carriers (ATX-NLC) was melt-emulsification, and these were optimized using factorial design and further evaluated for diverse parameters. Neurotoxicity was induced in rats by haloperidol. The treated and non-treated rats were then witnessed for their behaviour. TBARs and GSH levels were also determined. Pharmacokinetics was studied via HPLC.
Results: The average particle size (by DLS), entrapment efficiency and zeta potential of optimized ATX-NLC were 225.6 ± 3.04 nm, 65.91 ± 1.22% and -52.64 mV, respectively. Astaxanthin release (after 24 h in simulated nasal fluid) from optimized ATX-NLC was 92.5 ± 5.42%. Its thermoreversible nasal gel (ATX-NLC in-situ gel) was prepared using poloxamer-127. The obtained gel showed in-vivo betterment in the behaviour of animals when studied using the rotarod and akinesia test. Pharmacokinetic studies showed better availability of astaxanthin in the brain on the rats treated with ATX-NLC in-situ gel as compared to those treated with ATX-in-situ gel.
Conclusion: Astaxanthin-loaded lipidic nanoparticulate gel can be a hopeful adjuvant therapy for Parkinsonism and holds scope for future studies.
Keywords: Nose to brain delivery, in-situ gel, astaxanthin, nanostructured lipid carriers, motor imbalance, neuroprotection.
Graphical Abstract
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