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2000
Volume 20, Issue 7
  • ISSN: 1574-8855
  • E-ISSN: 2212-3903

Abstract

Background

Those who suffer from migraines, a neurological illness characterized by unilateral pulsating headaches, may find their daily activities impaired. Migraine sufferers often experience non-selective symptoms after taking an oral administration, such as discomfort, nausea, vomiting, and in rare circumstances, auras. The elastic nanovesicles work well as drug-delivery vehicles across the nasal passages and into the brain. Despite kynurenic acid's (KNA) potential as a neuroprotective drug, because of its poor capacity to penetrate the BBB, it has very limited use in therapeutic settings. This is why different drug delivery strategies to deliver KNA to the brain are being explored. This research intended to optimize KNA’s solubility, bioavailability, and penetration across the nasal mucosa for intranasal administration by formulating and evaluating KNA-loaded spanlastics (KNA-SPLs).

Objectives

Due to its enormous surface area, permeable endothelium membrane, abundant blood flow, ability to avoid first-pass metabolism, and convenience, the nasal mucosa is a promising target for drug delivery. making it an ideal site for drug absorption. The purpose of this investigation was to create KNA-SPLs and KNA spanlastic gel with this information in mind.

Methods

After creating the KNA-SPLs with thin-film hydration, a Box-Behnken design (BBD) was used for optimization. The PDI, zeta potential, vesicle size, entrapment efficiency, and drug release of the KNA-SPLs optimized formulation were evaluated. In addition to pharmacodynamics, confocal scanning laser microscopy (CLSM), and transmission electron microscopy (TEM), researchers looked into the nasal cavity and the brain. KNA-SPLs were prepared as a part of the Carbopol 934P and HPMC K4M liquid gelling system for gelation. The gelling duration, gelling capacity, and viscosity of the resulting solution were evaluated over two pH ranges (5 and 6).

Results

The vesicles' average diameters varied from 102.46 ± 7.68 to 254.31 ± 5.03 nm. The best nano-spanlastic formulation (F3) showed excellent EE% (61.27 ± 0.51%), PDI (0.156 ± 0.01), zeta potential (-29.43 ± 0.38), and drug release > 80%. The ingredients were as follows: phospholipon 90G 70mg, span 60 mg, and tween 80 mg and 75 mg. For sustained release and bio-distribution, the gelling time (3.240.28) and dissolution rate (> 50% within 24 min) of the produced nasal gel (G5) containing 1% Carbopol and 4% HPMC were much lower. Studies on animals have shown that intranasal treatment significantly increases the pace and extent of brain and plasma absorption, showing a high efficiency for targeting the brain. Pharmacodynamic studies involving Swiss albino mice have corroborated that the treatment formulation crossed the blood-brain barrier, adding credence to the drug's much improved anti-migraine capacity.

Conclusion

When compared to the conventional gel formulations, intranasal administration of KNA has been shown to be feasible with the use of spanlastics. The use of intranasal drug administration to deliver KNA has been reported to be mostly successful. This study demonstrates the efficacy of KNA-SPLs in treating migraine by targeting the brain.

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2025-12-03

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/content/journals/cdth/10.2174/0115748855264862231005182145
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Spanlastics for Nose-to-brain Delivery of Kynurenic Acid for Migraine: Design, Development and Preclinical Assessment
Curr Drug Ther 20, 1079 (2025); https://doi.org/10.2174/0115748855264862231005182145
/content/journals/cdth/10.2174/0115748855264862231005182145
/content/journals/cdth/10.2174/0115748855264862231005182145
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  • Article Type:     Research Article
Keyword(s): blood-brain distribution; box-behnken design; confocal scanning laser microscopy; Kynurenic acid; nasal permeation investigation; nose-to-brain drug transport; spanlastics

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