Browsing by Subject "Phospholipids"
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Item Development of an inhalational formulation of Coenzyme Q₁₀ to treat lung malignancies(2011-12) Carvalho, Thiago Cardoso; McConville, Jason ThomasCancer is the second leading cause of death in the United States and its onset is highly incident in the lungs, with very low long-term survival rates. Chemotherapy plays a significant role for lung cancer treatment, and pulmonary delivery may be a potential route for anticancer drug delivery to treat lung tumors. Coenzyme Q₁₀ (CoQ₁₀) is a poorly-water soluble compound that is being investigated for the treatment of carcinomas. In this work, we hypothesize that formulations of CoQ10 may be developed for pulmonary delivery with a satisfactory pharmacokinetic profile that will have the potential to improve a pharmacodynamic response when treating lung malignancies. The formulation design was to use a vibrating-mesh nebulizer to aerosolize aqueous dispersions of CoQ₁₀ stabilized by phospholipids physiologically found in the lungs. In the first study, a method was developed to measure the surface tension of liquids, a physicochemical property that has been shown to influence the aerosol output characteristics from vibrating-mesh nebulizers. Subsequently, this method was used, together with analysis of particle size distribution, zeta potential, and rheology, to further evaluate the factors influencing the capability of this nebulizer system to continuously and steadily aerosolize formulations of CoQ₁₀ prepared with high pressure homogenization. The aerosolization profile (nebulization performance and in vitro drug deposition of nebulized droplets) of formulations prepared with soybean lecithin, dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC) and distearoylphosphatidylcholine (DSPC) were evaluated. The rheological behavior of these dispersions was found to be the factor that may be indicative of the aerosolization output profile. Finally, the pulmonary deposition and systemic distribution of CoQ₁₀ prepared as DMPC, DPPC, and DSPC dispersions were investigated in vivo in mice. It was found that high drug amounts were deposited and retained in the mouse lungs for at least 48 hours post nebulization. Systemic distribution was not observed and deposition in the nasal cavity occurred at a lower scale than in the lungs. This body of work provides evidence that CoQ₁₀ may be successfully formulated as dispersions to be aerosolized using vibrating-mesh nebulizers and achieve high drug deposition in the lungs during inhalation.Item Effects of storage conditions on phospholipid content and TBA values in blends of beef and pork(Texas Tech University, 1980-12) Zolfaghari, RezaNot availableItem Enzyme catalyzed synthesis of structured phospholipids with conjugated linoleic acid and plant sterols(Texas A&M University, 2006-08-16) Hossen, Md MonjurStructured phospholipids with functional ingredients like conjugated linoleic acid (CLA) and plant sterols to deliver their physiological effects in different food formulations were synthesized. The lipase and phospholipase A2 catalyzed enzymatic acidolysis reaction between phospholipids (PLs) and CLA was used for fatty acid modification, while the phospholipase D catalyzed transphosphatidylation reaction between PLs and sterol was used for head group modification. Enzymatic processes were an effective way to produce structured phospholipids. Screening of four lipases and immobilized phospholipase A2 and combination of lipase and phospholipase showed that only Lipozyme RM IM and Lipozyme TL IM were effective in incorporation of CLA into PLs. The maximum incorporation achieved by the latter enzyme was 16% with soy PLs in 72 h. The class of phospholipids had a significant effect on the rate of incorporation of CLA compare to source of PLs. A method capable of predicting the rate of incorporation of CLA into phospholipids was developed using response surface methodology. A three-level four-factor Central Composite Rotatable Design (CCRD) was used. The four factors selected were lipase dosage (Ed, wt.% of substrate), substrate ratio (Sr,mol%), reaction time (ti, h) and reaction temperature (Te,oC). The enzyme load and substrate ratio had a greater effect on the rate of incorporation than did reaction time and temperature. A polynomial regression equation was developed to predict the reaction rate. The new phosphatidyl derivative, phosphatidyl-sitosterol, was found to be synthesized by the transfer reaction of phosphatidyl residue from phosphatidylcholine to β-sitosterol by phospholipase D from Streptomyces sp. in biphasic medium. The novel phosphatidyl .sitosterol derivative was identified by MALDI-TOF mass spectrometry. Plant sterols were modified to a more polar lipid class by synthesizing phospholipid derivatives of them. When these structured phospholipids were added to a whey protein based oil-in-water emulsion, the CLA incorporated structured phospholipids (CLA-PL) had higher heat stability and oxidative stability compared to the controls.Item Indicators of spoilage in Thuringer sausage(Texas Tech University, 1985-12) Subsoontorn, SirisopitNOT AVAILABLEItem Phospholipid headgroup superlattice modulation of cardiac calcium channel activity(Texas Tech University, 2000-08) Cannon, Brian L.The plasma membrane of cells consists of phospholipids, sterols, and proteins and maintains a steady composition through a regulatory mechanism that remains largely unknown. The interactions that occur among the membrane constituents are complex and are involved in compositional control. Among the proteins embedded is a class of transmembrane proteins called ion channels, specifically, the ryanodine receptors located in the sarcoplasmic reticulum of myocytes. These channels are responsible for the release of Ca ions, necessary for the activation of myofilaments to produce contractions. The receptors, through a process known as gating, undergo changes in conformation during the transition between open and closed states. Since proteins are surrounded by lipids and change conformations, the lipid-protein interactions must influence the protein state by hydrophobic coupling or on the headgroup level. By reconstituting the channels in planar lipid bilayers composed of two phospholipids with differing headgroup sizes, POPE and POPC and varying the ratio of the two lipids that form the bilayer, the channel functioned as sensors to determine how bilayer changes affect the channel. A peak in channel activity was observed over a narrow region of high PE:PC bilayers, indicating that lipid-protein interactions do have an important role in channel function. The results are interpreted as reflecting lateral organization by the lipids on the headgroup level in order to minimize the stress across the bilayer due to deformation, curvature, and packing, providing a favorable condition for the channel to enter its preferred conformation.Item Phospholipids and Terpenes Enhance the Absorption of Polyphenolics in a Caco-2 Cell Model(2010-08-30) Cardona Ponce, Jorge 1983-Anthocyanins are the most important class of water-soluble pigments responsible for red to blue colors in various plants. Anthocyanins naturally occur in a broad range of plants and studies have shown associations between fruit consumption and reduction of certain diseases thought to be related to the presence of these and other polyphenolics. However, anthocyanin absorption is fairly poor which hinders their potential to be utilized in the human body. Absorption of anthocyanins extracted from a?a? puree and port wine was assessed. Various combinations of terpenes and phospholipids were added to anthocyanins to modulate and increase their transport within a model system. A?a? and port wine anthocyanins were poorly transported in the absence of phospholipids and terpenes. The addition of terpenes and phospholipids significantly increased the transport of anthocyanins. Additionally, the presence of phospholipids and terpenes did not influence the way anthocyanins degraded over a 40 day period of time at three different temperatures. Transport of anthocyanins was not dependent on dosage since absorption results were similar at both concentrations of anthocyanins tested. Two methods to mix anthocyanins, phospholipids, and terpenes were also assessed (Sonication and French Press). Comparisons illustrated that both technologies created matrices that maintained the properties of phospholipids and terpenes as transport enhancers. Finally, a study to determine the efficacy of phospholipids and terpenes on a different type of polyphenolic compound was assessed. Transport of gallic acid was enhanced by the use of these agents that cemented the idea that phospholipids and terpenes can enhance the transport of various types of polyphenolics. The aiding effect of phospholipids and terpenes was well established and could play an important role in future investigation in this field. Further research needs to be conducted to reveal more information about the nature of these vesicles or associations that phospholipids and terpenes may have with anthocyanins. In vivo studies need to be considered to confirm these effects in rat models and, ideally, in humans. Nevertheless, these findings open a new line of investigation that could harvest promising results for the future of ingredient development for food products.Item Studies on Plasma Membrane Proteins Involved in Membrane Traffic: Syntaxins and E-Syts(2007-05-22) Min, Sang-Won; Sudhof, Thomas C.Fusion of synaptic vesicles is catalyzed by SNARE complex assembly which requires that the SNARE proteins syntaxin-1A and -1B, two isoforms of syntaxin-1, switch from a 'closed' to an 'open' conformation. To test the physiological significance of this switch, I analyzed mutant mice with a point mutation in syntaxin-1B which renders it predominantly 'open' in the syntaxin-1A null background. Whereas deletion of syntaxin-1A caused no detectable phenotype, opening of syntaxin-1B produced lethal epilepsy, independent of the presence of syntaxin-1A. Morphological and electrophysiological analyses revealed that opening of syntaxin-1B impaired steps in exocytosis upstream of vesicle priming, but enhanced Ca2+