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

Document Type: Research article

Authors

1 School of Pharmaceutical Sciences, Siksha ‘O’ Anusandhan University, Khandagiri Square, Bhubaneswar, Orissa, India.

2 Department of Pharmacology, Parul Institute of Pharmacy and Research, Vadodara, Gujarat, India.

3 Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Delhi-110054, India.

4 Department of Pharmaceutics, MS University, TIFAC Core, Vadodara, India.

Abstract

Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), showed very promising
neuroprotection action, but it suffers from high first pass metabolism and limited ability
to cross blood brain barrier. Severe gastric toxicity following oral administration further
limits its utility. Hence, the aim of this study was to investigate whether ibuprofen loaded
mucoadhesive microemulsion (MMEI) could enhance the brain uptake and could also protect
the dopaminergic neurons from MPTP-mediated neural inflammation. In this work, ibuprofen
loaded polycarbophil based mucoadhesive microemulsion (MMEI) was developed by using
response surface methodology (RSM). Male C57BL/6 mice were intranasally given 2.86 mg
ibuprofen/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 immunohistochemistry
was 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 for
nasal application. The result showed very significant effect (p < 0.05) of all three independent
variables on the responses of the developed MMEI. Noticeable improvement in motor
performance with spontaneous behavior was observed. TH neurons count in substantia nigra
with the density of striatal dopaminergic nerve terminals after MMEI administration. Results
of this study confirmed neuroprotection action of ibuprofen through intranasal MMEI against
MPTP induced inflammation in dopaminergic nerves in animal model and hence, MMEI can
be useful for prevention and management of Parkinson disease (PD).

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