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Research Article

Neuroprotection effects of kynurenic acid-loaded micelles for the Parkinson’s disease models

, , , , &
Received 31 Jan 2024, Accepted 18 Apr 2024, Published online: 23 May 2024
 

Abstract

Anti-glutamatergic agents may have neuroprotective effects against excitotoxicity that is known to be involved in the pathogenesis of Parkinson’s disease (PD). One of these agents is kynurenic acid (KYNA), a tryptophan metabolite, which is an endogenous N-methyl-D-aspartic acid (NMDA) receptor antagonist. However, its pharmacological properties of poor water solubility and limited blood–brain barrier (BBB) permeability rules out its systemic administration in disorders affecting the central nervous system. Our aim in the present study was to investigate the neuroprotective effects of KYNA-loaded micelles (KYNA-MICs) against PD in vitro and in vivo. Lipid-based micelles (MICs) in conjunction with KYNA drug delivery have the potential to enhance the penetration of therapeutic drugs into a diseased brain without BBB obstacles. KYNA-MICs were characterized by particle size (105.8 ± 12.1 nm), loading efficiency (78.3 ± 4.23%), and in vitro drug release (approximately 30% at 24 h). The in vitro experiments showed that KYNA-MICs effectively reduced 2-fold protein aggregation. The in vivo studies revealed that KYNA was successfully delivered by 5-fold increase in neurotoxin-induced PD brains. The results showed significant enhancement of KYNA delivery into brain. We also found that the KYNA-MICs exhibited several therapeutic effects. The KYNA-MICs reduced protein aggregation of an in vitro PD model, ameliorated motor functions, and prevented loss of the striatal neurons in a PD animal model. The beneficial effects of KYNA-MICs are probably explained by the anti-excitotoxic activity of the treatment’s complex. As the KYNA-MICs did not induce any appreciable side-effects at the protective dose applied to a chronic PD mouse model, our results demonstrate that KYNA provides neuroprotection and attenuates PD pathology.

Acknowledgements

The authors thank the Microscopy Center at Chang Gung University for technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Date are contained within this article.

Additional information

Funding

This research work was supported by the National Science and Technology Council (NSTC), Taiwan under Grant [number 109–2221-E-182–008-MY3]; the Chang Gung University, Taiwan under Grant [number UMRPD1N0081]; and Chang Gung Memorial Hospital, Taiwan under Grant [number CMRPG3M144].

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