27 research outputs found
Water dispersible microbicidal cellulose acetate phthalate film
BACKGROUND: Cellulose acetate phthalate (CAP) has been used for several decades in the pharmaceutical industry for enteric film coating of oral tablets and capsules. Micronized CAP, available commercially as "Aquateric" and containing additional ingredients required for micronization, used for tablet coating from water dispersions, was shown to adsorb and inactivate the human immunodeficiency virus (HIV-1), herpesviruses (HSV) and other sexually transmitted disease (STD) pathogens. Earlier studies indicate that a gel formulation of micronized CAP has a potential as a topical microbicide for prevention of STDs including the acquired immunodeficiency syndrome (AIDS). The objective of endeavors described here was to develop a water dispersible CAP film amenable to inexpensive industrial mass production. METHODS: CAP and hydroxypropyl cellulose (HPC) were dissolved in different organic solvent mixtures, poured into dishes, and the solvents evaporated. Graded quantities of a resulting selected film were mixed for 5 min at 37°C with HIV-1, HSV and other STD pathogens, respectively. Residual infectivity of the treated viruses and bacteria was determined. RESULTS: The prerequisites for producing CAP films which are soft, flexible and dispersible in water, resulting in smooth gels, are combining CAP with HPC (other cellulose derivatives are unsuitable), and casting from organic solvent mixtures containing ≈50 to ≈65% ethanol (EtOH). The films are ≈100 µ thick and have a textured surface with alternating protrusions and depressions revealed by scanning electron microscopy. The films, before complete conversion into a gel, rapidly inactivated HIV-1 and HSV and reduced the infectivity of non-viral STD pathogens >1,000-fold. CONCLUSIONS: Soft pliable CAP-HPC composite films can be generated by casting from organic solvent mixtures containing EtOH. The films rapidly reduce the infectivity of several STD pathogens, including HIV-1. They are converted into gels and thus do not have to be removed following application and use. In addition to their potential as topical microbicides, the films have promise for mucosal delivery of pharmaceuticals other than CAP
ε/ζ systems: their role in resistance, virulence, and their potential for antibiotic development
Cell death in bacteria can be triggered by activation of self-inflicted molecular mechanisms. Pathogenic bacteria often make use of suicide mechanisms in which the death of individual cells benefits survival of the population. Important elements for programmed cell death in bacteria are proteinaceous toxin–antitoxin systems. While the toxin generally resides dormant in the bacterial cytosol in complex with its antitoxin, conditions such as impaired de novo synthesis of the antitoxin or nutritional stress lead to antitoxin degradation and toxin activation. A widespread toxin–antitoxin family consists of the ε/ζ systems, which are distributed over plasmids and chromosomes of various pathogenic bacteria. In its inactive state, the bacteriotoxic ζ toxin protein is inhibited by its cognate antitoxin ε. Upon degradation of ε, the ζ toxin is released allowing this enzyme to poison bacterial cell wall synthesis, which eventually triggers autolysis. ε/ζ systems ensure stable plasmid inheritance by inducing death in plasmid-deprived offspring cells. In contrast, chromosomally encoded ε/ζ systems were reported to contribute to virulence of pathogenic bacteria, possibly by inducing autolysis in individual cells under stressful conditions. The capability of toxin–antitoxin systems to kill bacteria has made them potential targets for new therapeutic compounds. Toxin activation could be hijacked to induce suicide of bacteria. Likewise, the unique mechanism of ζ toxins could serve as template for new drugs. Contrarily, inhibition of virulence-associated ζ toxins might attenuate infections. Here we provide an overview of ε/ζ toxin–antitoxin family and its potential role in the development of new therapeutic approaches in microbial defense
Reversed Micelles as Microreactors: N-terminal Acylation of RNase A and its Characterization
Pricing European Options under Fractional Black–Scholes Model with a Weak Payoff Function
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
Characterization of Lipid A Variants by Energy-Resolved Mass Spectrometry: Impact of Acyl Chains
Continuity and continuous multi-utility representations of nontotal preorders: some considerations concerning restrictiveness
A continuous multi-utility fully represents a not necessarily total preorder on a topological space by means of a family of continuous increasing functions. While it is very attractive for obvious reasons, and therefore it has been applied in different contexts, such as expected utility for example, it is nevertheless very restrictive. In this paper we first present some general characterizations of the existence of a continuous order-preserving function, and respectively a continuous multi-utility representation, for a preorder on a topological space. We then illustrate the restrictiveness associated to the existence of a continuous multi-utility representation, by referring both to appropriate continuity conditions which must be satisfied by a preorder admitting this kind of representation, and to the Hausdorff property of the quotient order topology corresponding to the equivalence relation induced by the preorder. We prove a very restrictive result, which may concisely described as follows: the continuous multi-utility representability of all closed (or equivalently weakly continuous) preorders on a topological space is equivalent to the requirement according to which the quotient topology with respect to the equivalence corresponding to the coincidence of all continuous functions is discrete