Formulation, Optimization, in Vivo Pharmacokinetic, Behavioral and Biochemical Estimations of Minocycline Loaded Chitosan Nanoparticles for Enhanced Brain Uptake
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概要
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The minocycline hydrochloride (MH), at higher doses, is useful in the treatment of neurodegenerative disorders and owing to its antioxidant potential, it may have nootropic effects. MH loaded nanoparticles (MHNP) were coated with tween 80 (cMHNP) to improve its brain uptake followed by their optimization employing two factor-three level (32) central composite design (CCD) in order to minimize particle size and maximize drug entrapment efficiency (DEE) and validated. The optimized formulations were further subjected to in vitro drug release study; in vivo biodistribution studies in male wistar rats. The pharmacodynamic study was carried out using elevated plus maze (EPM) and Morris water maze (MWM) behavioral models for nootropic activity in swiss albino mice; and biochemical estimations (acetylcholine esterase, reduced glutathione, malondialdehyde and brain nitrite level). After intravenous (i.v.) administration, the concentration of MH in brain of cMHNP (6.21±0.64 µg/mL) treated rats was significantly higher with MH solution treated (0.70±0.06 µg/mL) as well as MHNP (1.03±0.12 µg/mL) treated animals. Pharmacodynamic studies revealed a significant improvement in memory of MH, MHNP and cMHNP treated swiss albino mice than saline treated control group. However, cMHNP revealed maximum decrease in transfer latency (TL) in EPM and maximum increase in time spent in target quadrant (TSTQ) in MWM. Although cMHNP did not produce significant change in brain acetylcholinesterase, but, significantly increased reduced glutathione, malondialdehyde and reduced brain nitrite level as compared to saline, MH solution and MHNP treated groups. The results suggest that cMHNP is a promising candidate for improved brain uptake of MH with better nootropic effect.
著者
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Mishra Dina
Department Of Pharmaceutical Sciences Guru Jambhesh War University
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Mishra Dina
Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology
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Singh Shailendra
Department of Chemistry, University of Delhi
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Nagpal Kalpana
Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology
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