Appraisal of Nano-Lipidic Astaxanthin cum Thermoreversible Gel and its Efficacy in Haloperidol Induced Parkinsonism

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: 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 thermo-reversible 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 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.

Neuroprotective Effect of Ultrasound Triggered Astaxanthin Release Nanoparticles on Early Brain Injury After Subarachnoid Hemorrhage

“…Nanomedicine improves the pharmacokinetics, administration, and bioavailability of drugs through biodegradable nano aggregates. At present, there are many kinds of nano delivery systems ( Gautam et al, 2021 ), including ATX lipid carrier (LBC) and ATX polymer system, to enhance the stability, hydrophilicity, and antioxidant capacity of ATX ( Tamjidi et al, 2018 ). However, in the treatment of central nervous system diseases, the existence of BBB hinders the delivery of most drugs to the brain.…”

Research progress of Astaxanthin nano-based drug delivery system: Applications, prospects and challenges?

“…ASX nano-pharmaceutics are promising to overcome these limitations and improve drug performance ( Fakhri et al, 2019 ). The ASX thermosreversible nasal gel (ATX-NLC in situ gel) prepared by adding poloxamer-127 to ASX nanostructured liposomes can enhance the transport and release of ASX in the brain, and can become an auxiliary treatment drug for Parkinson’s disease ( Gautam et al, 2021 ). ASX nanoparticles (Fe3O4/ATX/Transferrin NPs) coated with transferrin and polyethylene glycol (PEG) have good water dispersibility and biocompatibility.…”

Pharmacokinetics and Pharmacodynamics of Intranasal Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Nose-to-Brain Delivery

“…Tests used for assessing depression include the tail suspension, the forced swimming [ 91 ], the locomotor activity [ 92 ], and the marble-burying tests [ 93 ]. Models used for Parkinson’s disease include 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease [ 94 ], 6-hydroxydopamine partially lesioned rats [ 95 ], chlorpromazine-induced Parkinsonism-like signs [ 96 ], haloperidol-induced catalepsy [ 97 ], and rotenone-induced Parkinson’s disease [ 98 ].…”

“…In a recent study, astaxanthin-loaded NLCs were developed to improve the treatment of Parkinson’s disease [ 97 ]. The optimized NLC formulation was incorporated in an in situ gel composed of 20% Poloxamer 407 and 0.5% CS.…”