β-Cyclodextrin-crosslinked synthetic neuropeptide Y-based nanosponges in epilepsy by contributing GABAergic signal

Neuropeptide Y (NPY) is a polypeptide sequence useful in regulating physiological functions like homeostasis, feeding, etc., but its usage is restricted due to its short half-life. β-cyclodextrin-crosslinked nanosponges improve the drug release and stability due to its wide cavity, which is helpful to deliver therapeutics. The present work aimed to formulate synthetic NPY-based nanocarriers as sponges by polymer condensation mechanism using design experiment to improve the peptide release and stability. The validated nanosponges exhibited a particle size of 423.42 ± 5.32 nm, 75.82 ± 7.43 % entrapment efficiency and 83.50 ± 6.54 % NPY release for 24 h. The NPY and β-cyclodextrin interaction was confirmed by X-ray diffraction, Fourier transform infrared and nuclear magnetic resonance spectroscopy. The NPY-loaded nanosponges were found stable for 6 months at two conditions (5 ± 2 °C and 25 ± 2 °C). The cross-linked nanocarriers of synthetic peptide-based nanosponges powder at different doses were administered intranasally using a metered-dose inhaler in the animal model to check its antiepileptic activity. The synthetic NPY-loaded nanosponges at higher doses showed significant antiepileptic effects equivalent to the standard drug (administered orally) in maximal electroshock and chemically-induced seizures with an increase of NPY in the brain directly proportional to GABAergic signalling by increase in GABA levels resulting in convulsions attenuation.