Preclinical Study of Ibuprofen Loaded Transnasal Mucoadhesive Microemulsion for Neuroprotective Effect in MPTP Mice Model

Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), showed very promisingneuroprotection action, but it suffers from high first pass metabolism and limited abilityto cross blood brain barrier. Severe gastric toxicity following oral administration furtherlimits its utility. Hence, the aim of this study was to investigate whether ibuprofen loadedmucoadhesive microemulsion (MMEI) could enhance the brain uptake and could also protectthe dopaminergic neurons from MPTP-mediated neural inflammation. In this work, ibuprofenloaded polycarbophil based mucoadhesive microemulsion (MMEI) was developed by usingresponse surface methodology (RSM). Male C57BL/6 mice were intranasally given 2.86 mgibuprofen/kg/day for 2 consecutive weeks, which were pre-treated with four MPTP injections(20 mg/kg of body weight) at 2 h interval by intraperitoneal route and immunohistochemistrywas performed. Globule size of optimal MMEI was 46.73 nm ± 3.11 with PdI value as 0.201 ±0.19. Histological observation showed that optimal MMEI was biocompatible and suitable fornasal application. The result showed very significant effect (p < 0.05) of all three independentvariables on the responses of the developed MMEI. Noticeable improvement in motorperformance with spontaneous behavior was observed. TH neurons count in substantia nigrawith the density of striatal dopaminergic nerve terminals after MMEI administration. Resultsof this study confirmed neuroprotection action of ibuprofen through intranasal MMEI againstMPTP induced inflammation in dopaminergic nerves in animal model and hence, MMEI canbe useful for prevention and management of Parkinson disease (PD).