Intranasally administered melatonin core-shell polymeric nanocapsules: A promising treatment modality for cerebral ischemia

Aims: The neurohormone melatonin (MEL) has been reported as a promising neuroprotective molecule, however it suffers pharmaceutical limitations such as poor solubility and low bioavailability, which hinder its pharmacological and clinical potential. In the current work, MEL was loaded in core-shell nanocarrier system; polymeric nanocapsules (PNCs), and assessed for its potential in cerebral ischemia reperfusion injury rat model when administered intranasally. Key findings: Adopting a D-optimal factorial design, MEL-PNCs were successfully formulated using the nanoprecipitation technique. MEL-PNCs exhibited a particle size ranging from 143.5 to 444 nm, negative zeta potential values ranging from -24.2 to -38.7 mV, cumulative release % for MEL ranging from 36.79 to 41.31 % over 8 h period, with overall good storage properties. The selected MEL-PNCs formulation displayed 8-fold higher permeation than the drug solution across sheep nasal mucosa. MEL-PNCs administered intranasally decreased oxidative stress and hippocampal inflammation, and the histological examination revealed the significant restoration of hippocampal neurons. Significance: MEL-PNCs administered intranasally could be a promising treatment modality in brain ischemia.

Automated summary

This study successfully developed MEL-loaded polymeric nanocapsules (MEL-PNCs) and investigated their potential in neuroprotection in a rat model of cerebral ischemia reperfusion injury. The MEL-PNCs showed good drug release and permeation properties, and demonstrated a significant reduction in oxidative stress and inflammation caused by cerebral ischemia, leading to the restoration of hippocampal neurons.