Intranasal administration of thermoresponsive pterostilbene loaded nanoemulgel confers neuroprotection in a rat model of ischemic stroke.

PURPOSE: To develop and characterize Pterostilbene (PT)-loaded nanoemulgel (PNEG) and to evaluate its effect in rat model of ischemic stroke.

METHOD: PT-loaded nanoemulsion (PNE) was developed and further coated with chitosan and poloxamer-407 to obtain PNEG. It was characterized for particle size, zeta potential, morphology, entrapment efficiency, viscosity, stability, and ex-vivo mucoadhesive strength. Safety was assessed via in-vitro cytotoxicity assays and ex-vivo nasal mucosal compatibility. The therapeutic efficacy of PNEG was evaluated in a rat model of ischemic stroke, with assessments including neurobehavioral performances, oxidative stress, mitochondrial ultrastructure and complex activity, and pro-inflammatory cytokine levels.

RESULTS

PNEG exhibited particle size of 65.68 ± 0.66 nm with a zeta potential of 9.77 ± 1.2. The formulation demonstrated enhanced mucoadhesive strength and thermoresponsive viscosity, promoting prolonged nasal residence time. In-vitro and ex-vivo assessments confirmed the formulation's biocompatibility and non-toxicity. In-vivo, PNEG significantly enhanced neurological performance, including motor coordination, muscle strength, and cognition, while concurrently reducing oxidative stress, preserving mitochondrial integrity, and suppressing neuroinflammation in hippocampus and cortex of ischemic rats.

CONCLUSION

Intranasal PNEG enabled sustained PT delivery with robust neuroprotection in ischemic stroke, highlighting its promise as a clinically translatable strategy for targeted brain therapy.