Neuroprotective effects of novel nanosystems simultaneously loaded with vinpocetine and piracetam after intranasal administration.

ABSTRACT

AIMS: The study aim was to test the efficacy of a novel created hybrid nanosystem compared to other nanosystems in treatment of scopolamine induced memory impairment. MAIN METHODS: The fabrication and characterization of nanoformulations (microemulsion, liposomes, ethosomes, transfersomes and transethosomes) coencapsulating two cognitive enhancers; piracetam and vinpocetine delivered intranasally, in addition to a novel nanocomposite microemulsion/vesicular nanoformulation was described. KEY FINDINGS: Formulations delivered the drugs across sheep nasal mucosa, with cumulative percentage reaching 29.99% for vinpocetine and 57.78% for piracetam. While the solution form of the drugs was totally ineffective, the selected transethosomal, microemulsion and nanocomposite formulations reversed the scopolamine induced effect on the step through latency of passive avoidance test and the spontaneous alternation behavior in Y maze test, further confirmed by histopathlogical examination. All three nanoformulations significantly decreased the acetylcholinesterase activity and the extent of lipid peroxidation by 32-42%. The nanocomposite formulation was superior to the microemulsion and transethosomal formulations in its anti-inflammatory and antiapoptotic effects, delineated by higher extent of inhibition of COX-2 and caspase 3 expression respectively. SIGNIFICANCE: Results support the hypothesis that the novel microemulsion/vesicular nanocomposite system is a promising neuroprotective modality for intranasal brain targeting which is worthy of exploitation in other brain diseases.