Solubilisation of drugs within liposomal bilayers:alternatives to cholesterol as a membrane stabilising agent

Objectives The aim of this work was to investigate the effect of cholesterol on the bilayer loading of drugs and their subsequent release and to investigate fatty alcohols as an alternative bilayer stabiliser to cholesterol. Methods The loading and release rates of four low solubility drugs (diazepam, ibuprofen, midazolam and propofol) incorporated within the bilayer of multilamellar liposomes which contained a range of cholesterol (0–33 mol/mol%) or a fatty alcohol (tetradecanol, hexadecanol and octadecanol) were investigated. The molecular packing of these various systems was also investigated in Langmuir monolayer studies. Key findings Loading and release of drugs within the liposome bilayer was shown to be influenced by their cholesterol content: increasing cholesterol content was shown to reduce drug incorporation and inclusion of cholesterol in the bilayer changed the release profile of propofol from zero-order, for phosphatidyl choline only liposomes, to a first-order model when 11 to 33 total molar % of cholesterol was present in the formulation. At higher bilayer concentrations substitution of cholesterol with tetradecanol was shown to have less of a detrimental impact on bilayer drug loading. However, the presence of cholesterol within the liposome bilayer was shown to reduce drug release compared with fatty alcohols. Monolayer studies undertaken showed that effective mean area per molecule for a 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) : cholesterol mixture deviated by 9% from the predicted area compared with 5% with a similar DSPC : tetradecanol mixture. This evidence, combined with cholesterol being a much more bulky structure, indicated that the condensing influence of tetradecanol was less compared with cholesterol, thus supporting the reduced impact of tetradecanol on drug loading and drug retention. Conclusions Liposomes can be effectively formulated using fatty alcohols as an alternative bilayer stabiliser to cholesterol. The general similarities in the characteristics of liposomes containing fatty alcohols or cholesterol suggest a common behavioural influence for both compounds within the bilayer.

Selecting the most preferable alternatives in a group decision making problem using DEA

Group decision making is the study of identifying and selecting alternatives based on the values and preferences of the decision maker. Making a decision implies that there are several alternative choices to be considered. This paper uses the concept of Data Envelopment Analysis to introduce a new mathematical method for selecting the best alternative in a group decision making environment. The introduced model is a multi-objective function which is converted into a multi-objective linear programming model from which the optimal solution is obtained. A numerical example shows how the new model can be applied to rank the alternatives or to choose a subset of the most promising alternatives.

Progress in the development of in vitro human-based alternatives to animal models

Editorial

Public attitudes on the ethics of deceptively planting false memories to motivate healthy behavior

Researchers have proposed that planting false memories could have positive behavioral consequences. The idea of deceptively planting “beneficial” false memories outside of the laboratory raises important ethical questions, but how might the general public appraise this moral dilemma? In two studies, participants from the USA and UK read about a fictional “false-memory therapy” that led people to adopt healthy behaviors. Participants then reported their attitudes toward the acceptability of this therapy, via scale-rating (both studies) and open-text (Study 2) responses. The data revealed highly divergent responses to this contentious issue, ranging from abject horror to unqualified enthusiasm. Moreover, the responses shed light on conditions that participants believed would make the therapy less or more ethical. Whether or not deceptively planting memories outside the lab could ever be justifiable, these studies add valuable evidence to scientific and societal debates on neuroethics, whose relevance to memory science is increasingly acute.