Spanlastics for Nose-to-brain Delivery of Kynurenic Acid for Migraine: Design, Development and Preclinical Assessment
Authors: Chettupalli Ananda Kumar , Bodige Mounika , Jat Rakesh Kumar 
Published: February 2025

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).

Objective:
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 KNASPLs
and KNA spanlastic gel with this information in mind.

Method:
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 in vitro 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 in situ 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 nanospanlastic
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
60mg, and tween 80mg and 75mg. For sustained release and in vivo 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.