Potential of ceragenin CSA-13 and its mixture with pluronic F-127 as treatment of topical bacterial infections

Aims: Ceragenin CSA‐13 is a synthetic mimic of cationic antibacterial peptides, with facial amphiphilic morphology reproduced using a cholic acid scaffold. Previous data have shown that this molecule displays broad‐spectrum antibacterial activity, which decreases in the presence of blood plasma. However, at higher concentrations, CSA‐13 can cause lysis of erythrocytes. This study was designed to assess in vitro antibacterial and haemolytic activity of CSA‐13 in the presence of pluronic F‐127. Methods and Results: CSA‐13 bactericidal activity against clinical strains of bacteria associated with topical infections and in an experimental setting relevant to their pathophysiological environment, such as various epithelial tissue fluids and the airway sputum of patients suffering from cystic fibrosis (CF), was evaluated using minimum inhibitory and minimum bactericidal concentration (MIC/MBC) measurements and bacterial killing assays. We found that in the presence of pluronic F‐127, CSA‐13 antibacterial activity was only slightly decreased, but CSA‐13 haemolytic activity was significantly inhibited. CSA‐13 exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, including methicillin‐resistant strains, Pseudomonas aeruginosa present in CF sputa, and biofilms formed by different Gram (+) and Gram (?) bacteria. CSA‐13 bactericidal action is partially compromised in the presence of plasma, but is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage fluid. The synergistic action of CSA‐13, determined by the use of a standard checkerboard assay, reveals an increase in CSA‐13 antibacterial activity in the presence of host defence molecules such as the cathelicidin LL‐37 peptide, lysozyme, lactoferrin and secretory phospholipase A (sPLA). Conclusion: These results suggest that CSA‐13 may be useful to prevent and treat topical infection. Significance and Impact of the Study: Combined application of CSA‐13 with pluronic F‐127 may be beneficial by reducing CSA‐13 toxicity.     

PF127修饰的石墨烯复合材料的制备及其载药系统研究

实验制备负载阿霉素的PF127修饰的还原态石墨烯复合材料,并对其性能进行研究和评价。其方法是首先制备由弗朗尼克F127非共价功能化修饰的还原氧化石墨烯材料,记为PF127/GN,然后将该复合物对药物阿霉素进行负载,记为PF127/GN/DOX,并与未经阿霉素负载的纳米药物载体（PF127/GN）进行对比分析。观察其药物释放行为,细胞内递送过程和细胞毒性。研究发现,PF127/GN粒子大小为80μm左右,且粒子分布较均匀,厚度约增加至9.646μm;利用阿霉素对纳米载体进行负载之后,负载效果随药物浓度的增加而不断提高,负载在氧化石墨烯表面的阿霉素的释放行为可通过改变体系的pH值进行调节。负载了阿霉素的纳米药物载体能够发挥良好的释放作用,具有相对较强的生物毒性。因此经过阿霉素负载的PF127修饰的还原态石墨烯复合材料性能良好,具有广阔的应用前景。     

Lecithin organogels as a potential phospholipid-structured system for topical drug delivery: A review

The purpose of this review is to give an insight into the considerable potential of lecithin organogels (LOs) in the applications meant for topical drug delivery. LOs are clear, thermodynamically stable, viscoelastic, and biocompatible jelly-like phases, chiefly composed of hydrated phospholipids and appropriate organic liquid. These systems are currently of interest to the pharmaceutical scientist because of their structural and functional benefits. Several therapeutic agents have been formulated as LOs for their facilitated transport through topical route (for dermal or transdermal effect), with some very encouraging results. The improved topical drug delivery has mainly been attributed to the biphasic drug solubility, the desired drug partitioning, and the modification of skin barrier function by the organogel components. Being thermodynamically stable, LOs are prepared by spontaneous emulsification and therefore posses prolonged shelf life. The utility of this novel matrix as a topical vehicle has further increased owing to its very low skin irritancy potential. Varied aspects of LOs viz formation, composition, phase behavior, and characterization have been elaborated, including a general discussion on the developmental background. Besides a comprehensive update on the topical applications of lecithin organogels, the review also includes a detailed account on the mechanistics of organogelling. Published: October 6, 2005     

A polerovirus,Potato leafroll virus,alters plant–vector interactions using three viral proteins

Potato leafroll virus (PLRV), genus Polerovirus, family Luteoviridae, is a major pathogen of potato worldwide. PLRV is transmitted among host plants by aphids in a circulative–nonpropagative manner. Previous studies have demonstrated that PLRV infection increases aphid fecundity on, and attraction to, infected plants as compared to controls. However, the molecular mechanisms mediating this relationship are still poorly understood. In this study, we measured the impact of PLRV infection on plant–aphid interactions and plant chemistry in two hosts: Solanum tuberosum and Nicotiana benthamiana. Our study demonstrates that PLRV infection attenuates the induction of aphid-induced jasmonic acid and ethylene in S. tuberosum and N. benthamiana. Using transient expression experiments, insect bioassays and chemical analysis, we show that expression of three PLRV proteins (P0, P1, and P7) mediate changes in plant–aphid interactions and inhibition of aphid-induced jasmonic acid and ethylene in N. benthamiana. This study enhances our understanding of the plant-vector-pathogen interface by elucidating new mechanisms by which plant viruses transmitted in a circulative manner can manipulate plant hosts.     

Protection mechanisms of freely suspended animal cells (CRL 8018) from fluid-mechanical injury. Viscometric and bioreactor studies using serum, pluronic F68 and polyethylene glycol

We use bioreactor and viscometric studies to examine the mechanism by which three additives, fetal bovine serum (FBS), pluronic F68, and polyethylene glycol (PEG), protect the freely suspend CRL-8018 cells from damage due to interactions with bubbles in agitated bioreactors. In bioreactor studies, the protective effect of an addictive could be due to either changes in the ability of the cell resist shear (biological mechanism) or to changes in the medium properties that effect the level or frequency of forces experienced by the cells (physical mechanism). Bioreactor studies show that protection by all three addictives occurs whether the cells are grown in the presence of the addictives (long exposure) or the addictives are added to medium after the cells were exposed to detrimental agitation intensity (short exposure). In the viscometric studies, exposure of cells to laminar shear in the absence of gas-liquid interfaces assesses only the ability of the cells to resist a constant level of shear in a medium with or without an additive. Viscometric studies show that prolonged exposure to FBS makes the cells more shera tolerant, but that short (30-120 min) exposure to FBS does not affect their shear tolerance. We thus conclude that the protective effect of FBS in bioreactors id of both physical and biological nature. The biological contribution is metabolic in nature rather than fast acting. Viscometric studies show that either long or short exposure of the cells to either F68 or PEG does not make the cells more shear tolerant. WE therefore conclude that the protective effect of F68 and PEG does not make the cells more shear tolerant. We therefore conclude that the protective effect of F68 and PEG in bioreactors is physical in nature.     

Thermoreversible-mucoadhesive Gel for nasal delivery of sumatriptan

The purpose of the present study was to develop intranasal delivery systems of sumatriptan using thermoreversible polymer Pluronic F127 (PF 127) and mucoadhesive polymer Carbopol 934P (C934P). Formulations were modulated so as to have gelation temperature below 34°C to ensure gelation at physiological temperature after intranasal administration. Gelation temperature was determined by physical appearance as well as by rheological measurement. The gelation temperatures of the formulations decreased by addition of increasing concentrations of Carbopol (ie, from 29°C for 18% PF127 to 23.9°C for 18% PF127, 0.5% Carbopol). The mucoadhesive force in terms of detachment stress, determined using sheep nasal mucosal membrane, increased with increasing concentration of Carbopol. The results of in vitro drug permeation studies across sheep nasal mucosa indicate that effective permeation coefficient could be significantly increased by using in situ gelling formulation with Carbopol concentration 0.3% or greater. Finally, histopathological examination did not detect any damage during in vitro permeation studies. In conclusion, the PF 127 gel formulation of sumatriptan, with in situ gelling and mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption. Published: August 4, 2006     

基因工程疫苗的病毒载体

病毒基因工程疫苗是以活病毒为载体将一段外源基因导入机体细胞内,并使外源基因维持较高水平的表达。通过使用复制型或复制缺陷型载体能使表达的抗原诱生机体产生相应的体液抗体,并能引起机体产生细胞介导的免疫反应及粘膜免疫反应。本文主要介绍有可能用于基因工程疫苗的DNA及RNA病毒载体构建及其应用。