Preparation, characterization, and evaluation of liposomal ferulic acid in vitro and in vivo.
ABSTRACT In the present study, various gradients were evaluated for efficient loading of weak acid into liposomes. Several salt gradients showed efficient loading of ferulic acid (FA) into liposomes and the optimized conditions were established in calcium acetate gradient method to obtain 80.2 +/- 5.2% entrapment efficiency (EE). Unilamellar vesicles were observed in micrographs and liposomal FA showed good stability. 80% of FA was released from liposomes within 5 h in vitro. There is a novel finding in this study: that drugs could be entrapped with a high solubility in the intraliposomal buffer in contrast to the low solubility in the extraliposomal buffer. The results of body distribution in rats indicated that liposomes could improve the body distribution of FA. For FA liposome, the concentration of FA in brain was two-fold higher than that of free FA. Liposomal FA was a promising approach to improve the body distribution of FA.
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ABSTRACT: Amyloid precursor protein (APP) proteolysis is required for production of amyloid-β (Aβ) peptides that comprise β-amyloid plaques in brains of Alzheimer's disease (AD) patients. Recent AD therapeutic interest has been directed toward a group of anti-amyloidogenic compounds extracted from plants. We orally administered the brain penetrant, small molecule phenolic compound ferulic acid (FA) to the transgenic PSAPP mouse model of cerebral amyloidosis (bearing mutant human APP and presenilin-1 transgenes) and evaluated behavioral impairment and AD-like pathology. Oral FA treatment for 6 months reversed transgene-associated behavioral deficits including defective: hyperactivity, object recognition, and spatial working and reference memory, but did not alter wild-type mouse behavior. Furthermore, brain parenchymal and cerebral vascular β-amyloid deposits as well as abundance of various Aβ species including oligomers were decreased in FA-treated PSAPP mice. These effects occurred with decreased cleavage of the β-carboxyl-terminal APP fragment, reduced β-site APP cleaving enzyme 1 protein stability and activity, attenuated neuroinflammation, and stabilized oxidative stress. As in vitro validation, we treated well-characterized mutant human APP-overexpressing murine neuron-like cells with FA and found significantly decreased Aβ production and reduced amyloidogenic APP proteolysis. Collectively, these results highlight that FA is a β-secretase modulator with therapeutic potential against AD.PLoS ONE 01/2013; 8(2):e55774. · 3.53 Impact Factor
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ABSTRACT: The delayed onset of therapeutic outcomes is a major drawback of the current antidepressants. The blood-brain barrier is the most important bottleneck impeding drug transport into the brain. Therefore, development of novel antidepressant medications with rapid onset and sustained activity is urgent. RGD liposomes showed an excellent effect of brain-targeting drug delivery and increased the entering rate to the brain. In the present study, we prepared cyclic RGD liposomes loaded with edaravone (cRGD-ERLs) and evaluated the potential antidepressant-like effects of this drug delivery system in rats. The results showed single injection of cRGD-ERLs produced significant antidepressant-like effects in both forced swim and novelty suppressed feeding test. Moreover, acute cRGD-ERLs increased the expression of c-fos in the medial prefrontal cortex, suggesting that cRGD-ERLs could activate the neuronal function. Furthermore, cRGD-ERLs reversed the increase of lipopolysaccharides (LPS)-induced plasma cytokine IL-1β and IL-6, suggesting that normalization of cytokine level might be involved in the behavioral response of cRGD-ERLs. Finally, cRGD-ERLs prevented the increase of immobility induced by LPS in the forced swim test. Overall, the current data revealed a novel brain-target drug delivery system, which can be used to improve the therapeutic outcomes of antidepressants by increase of crossing rate to the brain.European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 04/2014; · 2.61 Impact Factor
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ABSTRACT: Recent studies have focused more on Chinese medicine used for the treatment of cerebrovascular disease. The current review covers researches on the pharmacokinetic of Chinese medicine, providing a convenient reference for researchers to increase efficiency of drug discovery, by compiling and discussing the pharmacokinetics of four classical Chinese medicines for therapy of cerebrovascular disease containing: Panax notoginseng, Salvia miltiorrhiza, Ligusticum Chuanxiong and Gardenia. It also helps to eliminate side effect as far as possible from inappropriate Chinese medicine usage. Current integrative and comprehensive review of Chinese medicine for cerebrovascular disease including 1) the absorption of some constituents is limited such as ginsenosides Rg1 and Rb1. It may be affected by gastric juice, first-pass effect etc. 2) the interactions between Chinese medicine and prescription can occur. Borneol and carbomer would enhance the absorption of R1 and Rg1 in vivo by increasing adjacent cell transport ability. 3) the distribution of active constituents in brain is important for cerebrovascular disease. BBB protects brain from xenobiotic. Intranasal, intra-tympanic administration is a promising alternative to conventional administration to reach brain for ligustrazine. 4) renal excretion is the uppermost route of these Chinese medicines. But biliary, faecal and urinary excretion are the other major routes. Theoretical and practical aspects are described with pharmacokinetics examples. In the end, this paper also discusses recent development of bio-analysis of Chinese medicine.Fitoterapia 04/2013; 88:50-75. · 2.23 Impact Factor