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Mol Neurobiol. 2016 Aug;53(6):3842-3853. doi: 10.1007/s12035-015-9333-9. Epub 2015 Jul 11.

Enhanced Neuroprotection of Acetyl-11-Keto-β-Boswellic Acid (AKBA)-Loaded O-Carboxymethyl Chitosan Nanoparticles Through Antioxidant and Anti-Inflammatory Pathways.

Author information

1
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
2
Department of Pharmaceutical Analysis, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
3
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
4
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. liyuwenzs@gmail.com.
5
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. adwen-2004@hotmail.com.

Abstract

Acetyl-11-keto-β-boswellic acid (AKBA), a main active constituent from Boswellia serrata resin, is a novel candidate for therapy of cerebral ischemia-reperfusion (I/R) injury. Nevertheless, its poor solubility in aqueous solvent, bioavailability, and rapid clearance limit its curative efficacy. To enhance its potency, in our study, AKBA-loaded o-carboxymethyl chitosan nanoparticle (AKBA-NP) delivery system was synthesized. The transmission electron microscopy and transmission electron microscope images of AKBA-NPs suggested that particle size was 132 ± 18 nm, and particles were spherical in shape with smooth morphology. In pharmacokinetics study, AKBA-NPs apparently increases the area under the curve of plasma concentration-time and prolonged half-life compared with AKBA. The tissue distribution study confirmed that AKBA-NPs had a better brain delivery efficacy in comparison with AKBA. The results from our pharmacodynamic studies showed that AKBA-NPs possess better neuroprotection compared with AKBA in primary neurons with oxygen-glucose deprivation (OGD) model and in animals with middle cerebral artery occlusion (MCAO) model. Additionally, AKBA-NPs modulate antioxidant and anti-inflammatory pathways more effectively than AKBA by increasing nuclear erythroid 2-related factor 2 and heme oxygenase-1 expression, and by decreasing nuclear factor-kappa B and 5-lipoxygenase expression. Collectively, our results suggest that AKBA-NPs serve as a potent delivery vehicle for AKBA in cerebral ischemic therapy.

KEYWORDS:

Boswellic acid; Cerebral ischemia; Nanoparticle; Neuroprotective effects; Pharmacokinetics

PMID:
26162321
DOI:
10.1007/s12035-015-9333-9
[Indexed for MEDLINE]

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