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: 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.Drug Development and Industrial Pharmacy 10/2010; 36(10):1186-94. DOI:10.3109/03639041003695097 · 2.01 Impact Factor
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ABSTRACT: The successful treatment of brain tumors or metastases in the brain is still hampered by the very efficient blood-brain barrier, which prevents the cerebral accumulation of a pharmacologically sufficient amount of a drug. Beside the possibility of disintegrating the functionality of this effective working barrier, a nanocarrier-mediated transport is presently an interesting and promising method to increase the drug concentration in the brain. Nanocarriers are small vesicles (<200 nm) and can be prepared by polymerization, resulting in nanoparticles, or by producing superficial lipid structures to incorporate the drug. In this context, liposomes are of importance owing to their ability to adapt their properties to the pharmacological requirements. In this article, we will give an overview of current possibilities of enhancing anticancer drug transport across the blood-brain barrier, based on its structure and functionality. Special consideration will be given to recent liposomal approaches that use active targeting for receptor-mediated transport across this physiological barrier.Expert Review of Clinical Pharmacology 07/2011; 4(4):477-90. DOI:10.1586/ecp.11.26
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ABSTRACT: Remote loading of liposomes by trans-membrane gradients is used to achieve therapeutically efficacious intra-liposome concentrations of drugs. We have developed Quantitative Structure Property Relationship (QSPR) models of remote liposome loading for a data set including 60 drugs studied in 366 loading experiments internally or elsewhere. Both experimental conditions and computed chemical descriptors were employed as independent variables to predict the initial drug/lipid ratio (D/L) required to achieve high loading efficiency. Both binary (to distinguish high vs. low initial D/L) and continuous (to predict real D/L values) models were generated using advanced machine learning approaches and 5-fold external validation. The external prediction accuracy for binary models was as high as 91-96%; for continuous models the mean coefficient R(2) for regression between predicted versus observed values was 0.76-0.79. We conclude that QSPR models can be used to identify candidate drugs expected to have high remote loading capacity while simultaneously optimizing the design of formulation experiments.Journal of Controlled Release 12/2011; 160(2):147-57. DOI:10.1016/j.jconrel.2011.11.029 · 7.26 Impact Factor