Polyoxyethylene with biological

Interactions of Nonionic Polyoxyethylene Alkyl and Aryl Ethers with Membranes and Other Biological Systems... 

It has been recognised for some time (see for example reference 1), that surfactants can increase the rate and extent of transport of solute molecules through biological membranes by fluidisation of the membrane. It is only recently, however, that sufficient work has been carried out to allow some analysis of structure-action relationships. In this overview an attempt is made, by reference to our own work and to work in the literature, to define those structural features in polyoxyethylene alkyl and aryl ethers which give rise to biological activity, especially as it is manifested in interactions with biomembranes and subsequent increase in the transport of drug molecules. 

The difficulty with HLB as an index of physicochemical properties is that it is not a unique value, as the data of Zaslavsky et al. (1) on the haemolytic activity of three alkyl mercaptan polyoxyethylene derivatives clearly show in Table 1. Nevertheless data on promotion of the absorption of drugs by series of nonionic surfactants, when plotted as a function of HLB do show patterns of behaviour which can assist in pin-pointing the necessary lipophilicity required for optimal biological activity. It is evident however, that structural specificity plays a part in interactions of nonionic surfactants with biomembranes as shown in Table 1. It is reasonable to assume that membranes with different lipophilicities will"require" surfactants of different HLB to achieve penetration and fluidization one of the difficulties in discerning this optimal value of HLB resides in the problems of analysis of data in the literature. For example, Hirai et al. (8 ) examined the effect of a large series of alkyl polyoxyethylene ethers (C4,C0, Cj2 and C 2 series) on the absorption of insulin through the nasal mucosa of rats. Some results are shown in Table II. 

Emanuele MR, Baleisubramanian M, AUudeen HS. Polyoxypropylene/polyoxyethylene copolymers with improved biological activity. Norcross, GA C3d Rx Corporation, 1996. 

Triton X-100 and X-114 are industrial p-rcrr-octylphenol polyoxyethylene surfactants with about 9.2 and 7.5 ethylene oxide groups per molecule respectively. They are used in biochemical studies because of their ability to disrupt biological membranes without denaturing integral membrane proteins [ 119]. TX-100 [ 120] forms an H1 phase between 37 and 63% surfactant from 0 to... 

NS Vs are defined as vesicular nonionic surfactant bilayers that enclose a space of aqueous solution. Recently, various surfactants have been used for the preparation of NS Vs. These surfactant molecules include polyoxyethylene al-kylethers [1], polyglycol alkylethers [2] and glucosyl dialkylethers [3], etc. In many pharmaceutical studies on NSVs, it was demonstrated that using NSVs allows a wide study of the influence of chemical composition on the physicochemical features and the biological fate of vesicles. The ability of NSVs to entrap various solutes and to interact with cells by endocytosis or fusion has led to their application as a vesicle for intracellular delivery [4]. The mean size and size distribution of vesicles were important factors affecting physicochemical stability. 

Inert ingredients are presumed to have no physical, chemical, or biological activity, but this is not always the case. Pesticide testing, required to register pesticides, is mostly performed with the active ingredient alone, not the complete formulation. Many of the so-called inert ingredients, of which there are currently about 3000 in use [24], are themselves toxic. Eor example, a commercial herbicide that contains glufosinate ammonium (GLA) as its active component and an anionic surfactant, sodium polyoxyethylene alkylether sulfate (AES), decreases blood pressure and alters the heart rates of rats. GLA alone does not affect either parameter, whereas AES alone does [25]. Xylene, used as a solvent in many pesticides, is a known human neurotoxin [26]. 

Experimental and mathematical modeling studies were performed to evaluate the potential benefits and limitations associated with the use of nonionic surfactants to enhance the microbial transformation of hexachlorobenzene (HCB) by a dechlorinating mixed culture enriched from a contaminated sediment. In general. Tween series surfactants were shown to have little impact on methanogenesis, whereas, polyoxyethylene (POE) alcohols, Triton X-100 and SDS were found to strongly inhibit methanogenesis and HCB dechlorination. Subsequent experiments conducted with Tween 80 illustrated the ability of this surfactant to enhance the solubility of HCB and to reduce the HCB-soil distribution coefficient. Model simulations demonstrated, however, that the aqueous phase mass fraction of HCB was substantially reduced in micellar solutions, which corresponded with observed reductions in HCB dechlorination. These results indicate that the impacts of surfactants on both biological activity and contaminant phase distributions should be evaluated in order to accurately assess the potential for biotransformation of hydrophobic contaminants in the presence of surfactants. 

Symmetrical (two equal fatty acid chains) (Figure 5.4, 1) and asymmetrical (two different fatty acid chains) (Figure 5.4, 2) nonionic double-chain surfactants of the type A ,A -diacyl lysine polyoxyethylene glycol amide compounds, with a structural resemblance to natural lecithin phospholipids, have been reported by the authors lab [35-38] to determine the effect of several structural parameters (hydrophobic chain length, polyoxyethylene (POE) chain length and number of polyoxyethylene chains) on the physicochemical properties and biological performance of these natural mimics. 

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