Preparation, Characterization, and Evaluation of Liposomal Ferulic Acid In Vitro and In Vivo
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.Drug Development and Industrial Pharmacy (Impact Factor: 2.1). 07/2008; 34(6):602-8. DOI: 10.1080/03639040701833559
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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- "The aqueous solubility of natural cyclodextrins is very poor, nevertheless it can be significantly improved by chemical substitutions at the 2, 3, and 6 hydroxyl sites. FA and GA have been encapsulated in lipophilic (liposomal, etc.) (Qin et al., 2008) and hydrophilic carriers (proteins, cyclodextrins, etc.) (da Rosa et al., 2013; Wang et al., 2011). Encapsulation of FA with HPbCD is reported to give a six fold increase in the solubility of FA whereas a threefold increase was observed for the FA/b-CD complex (Zhang et al., 2009). "
ABSTRACT: The complexes formed by two polyphenols, trans-Ferulic acid (FA) and Gallic acid (GA) with 2-hydroxypropyl-b-cyclodextrin (HPβCD), by the spray-drying method, were studied. Encapsulation-efficiencies (EE) of the complexes prepared were evaluated by HPLC. In the case of co-encapsulation, the EE of GA was lowered, whereas that of FA was almost stable, indicating a possible antagonistic relationship between the two phenols for the HPβCD cavity. The physicochemical characterization of the complexes was carried out by Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM). SEM observations revealed that the coencapsulated phenolic complex resulted in a more rounded shape outer surfaces of HPβCD than when encapsulated separately. FT-IR and DSC data indicated that the two polyphenols exhibit a possible interaction in the coencapsulated complex. The complexes showed no loss of their ability to scavenge DPPH radical relatively to the single agent at the concentrations used. Copyright © 2015. Published by Elsevier Ltd.
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- "Because the compound remains in the circulation longer than other naturally occurring compounds like vitamin C , FA is expected to stay in the body long enough to elicit its effects. While FA is not necessarily predicted to cross the blood-brain barrier due to it being a charged molecule with a hydroxyl group , others have detected the molecule in the rodent brain following peripheral administration . Additionally, an ethyl ester derivative of FA has been shown to protect neurons against amyloid β-peptide-induced oxidative stress and neurotoxicity . "
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.
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ABSTRACT: Pirarubicin (THP), an analogue of doxorubicin, has exhibited promising activities against acute leukemia, malignant lymphoma, and several solid tumors. However, the cumulative cardiotoxicity limits its wide application in chemotherapy. To provide an alternative strategy for reducing the cardiotoxicity, a novel THP liposome powder (L-THP), comprising distearoylphosphatidylcholine, distearoylphosphatidylglycerol, cholesterol, and lactose was appropriately prepared based on the physicochemical properties of THP. And L-THP was characterized and evaluated. Comparative studies on pharmacokinetic and biodistribution behaviors between L-THP and commercialized THP injection were performed in normal mice through intravenous administration. When L-THP was reconstituted in a proper amount of normal saline for injection, it had a mean diameter of around 220.0 nm, a zeta potential of about -33.0 mV, and a high THP entrapment efficiency of more than 93.1%. Pharmacokinetics study showed that heart accumulation of THP could be reduced by 81.2% for L-THP. These results suggest that our L-THP might greatly reduce the cardiotoxicity, thus improving the therapeutic index of THP. Meanwhile, further preclinical studies are warranted to define the cardiotoxicity and the therapeutic efficacy of L-THP.
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