The purpose of this research was to investigate the effects that aspirin (ASA) and its metabolites, salicylic acid (SA) and acetic acid (AA), have on the delivery of drugs across biological barriers when used in conjunction with electroporation. Electroporation is a technique used to enhance drug delivery across bio-membranes in which a transmembrane potential is induced into cellular membranes, resulting in the creation of aqueous pores that allow molecules to pass through the otherwise impermeable barrier. Aspirin is a widely used drug that has been used for over a century and has been proven relatively safe at normal doses as indicated by the low number of reports of poisoning cases it has been involved in. Components of aspirin are known to soften the cellular membranes by solubilizing the cell's surface proteins. B16F10 murine melanoma cancer cells were used in this investigation and treated with a 120µM buffered solution of calcein, a fluorescent indicator, in which the amount of delivered tracer molecules was measured using fluorescence. Identical concentrations of ASA and SA were investigated (1mM, 5mM, and 10mM) separately, focusing the effects concentration has electroporation delivery. Diluted acetic acid was also investigated at pH values of 6.42, 5.36, and 4.40. The concentration of acetic acid that had the lowest pH and ASA with the highest concentration had the greatest impacts on the augmentation of calcein delivery. Therefore, this demonstrates that aspirin and acetic acid have the potential to improve targeted molecular delivery in combination with electroporation.

The current increased use of antifungal agents has resulted in the development of resistance to these drugs. Search for new antifungals with different mechanisms of action overcoming the multidrug resistance is thus underway. Surface-active antifungals have the advantages of minimizing host toxicity and the emergence of drug resistance. We have developed a fluorescence method based on the use of the potentiometric fluorescent probe diS-C3(3), substrate of two major S. cerevisiae MDR pumps, Pdr5p and Snq2p. It allows us to monitor with high sensitivity and in real time changes in the activities of both pumps and also in membrane potential. We present here an efficient strategy for identifying pump inhibitors with minimal side effects on membrane integrity, and compare the potencies of different inhibitors towards MDR pumps. New efficient inhibitors of MDR pumps could potentially be used in conjunction with current antimicrobials that are MDR pump substrates. The method can be also used to determine the mechanism of action of surface-active drugs and their lowest effective concentrations.