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Liposomes have been prepared from dipalmitoylphosphatidylcholine (DPPC) incorporating the cationic lipids stearylamine (SA), dimethyldioctadecylammonium bromide (DDAB) and dimethylaminoethane carbamoyl cholesterol (DCchol) and the anionic lipids dipalmitoylphosphatidylglycerol (DPPG) and phosphatidylinositol (PI). Their adsorption to biofilms of skin-associated bacteria (Staphylococcus epidermidis and Proteus vulgaris) and oral bacteria (Streptococcus mutans and sanguis) has been investigated as a function of mole % cationic and anionic lipid. Targeting (adsorption) was most effective for the systems DPPC-chol-SA, DPPC-DPPG and DPPC-PI liposomes to S. epidermidis. The effect of extracellular mucopolysaccharide on targeting was investigated for S. epidermidis biofilms. It was found that targeting increased with the level of extracellular mucopolysaccharide for all liposome compositions studied. The delivery of the oil-soluble bactericide Triclosan and the water soluble bactericide chlorhexidine was studied for a number of liposomal compositions. Superior delivery of both bactericides relative to the free bactericide occurred for DPPC-chol-SA liposomes and for Triclosan delivery by DPPC-DPPG and DPPC-PI liposomes targeted to S. epidermidis at low bactericide concentrations. DPPC-chol-SA liposomes were also effective for delivery of Triclosan to S. sanguis biofilms. Double labelling experiments using [14C]-chlorhexidine and [3H]-DPPC suggested that there was exchange between adsorbed liposomes which had delivered bactericide to the biofilm and those in the bulk solution implying a diffusion mechanism for bactericide delivery.

Phospholipid liposomes have been prepared from phospholipid mixtures including dipalmitoylphosphatidylcholine/phosphatidylinositol (DPPC/PI) and DPPC/dipalmitoylphosphatidylglycerol (DPPC/DPPG) mixtures and targeted to adsorbed biofilms of the skin-associated bacteria Staphylococcus epidermidis and Proteus vulgaris and the oral bacterium Streptococcus sanguis. The effects of time, liposome concentration and density of bacteria in the biofilm have been studied in detail for Staphylococcus epidermidis. The targeting (as assessed by the apparent monolayer coverage of the biofilms by liposomes) to the biofilms was found to be sensitive to the mol% of PI and DPPG in the liposomes and optimum levels of PI were found for targeting to each bacterium. The use of PI and DPPG-containing liposomes for the delivery of the bactericide, Triclosan, to biofilms of Staphylococcus epidermidis was studied as a function of the amount of Triclosan carried by the liposomes. All the liposome systems tested inhibited the growth of bacteria from the biofilms after brief (2 min) exposure to Triclosan-carrying liposomes. At low Triclosan levels bacterial growth inhibition by Triclosan-carrying liposomes exceeded that by an equivalent level of free Triclosan. After short periods (min) of exposure of biofilms to Triclosan-carrying liposomes the bactericide was shown to preferentially concentrate in the biofilms relative to its liposomal lipid carrier. The results suggest that phospholipid liposomes with appropriately chosen lipid composition have potential for the targeting and delivery of bactericide to bacteria.

A theoretical model has been developed for the interaction of the surface polymers of the bacterial glycocalyx with liposomes incorporating lipids with polyhydroxy headgroups such as phosphatidylinositol (PI). The theory is based on a lattice model and equations are derived for the potential energy of interaction between the surfaces of a bacterium and a liposome as a function of their separation. It is shown that a relatively small energy of interaction, less than that of a single hydrogen bond, between the polyhydroxyl headgroup of the liposomal lipid and bacterium surface polymer residues could give rise to a potential energy of interaction in excess of the classical double layer repulsive force and attractive dispersion force interactions. The most important prediction of the theory is that the potential energy of interaction goes through a minimum as a function of the polyhydroxy lipid (PI) concentration in the liposomal surface, thus predicting an optimal liposomal composition for adsorption of liposome to bacterium. This result is in concordance with the adsorption of dipalmitoylphosphatidylcholine-PI liposomes to a range of biofilms of oral and skin-associated bacteria on solid supports, where optimum levels of PI for adsorption have been found. The theory demonstrates that subtle changes in the composition of liposomal and bacterial surfaces involving relatively small interaction energies can markedly influence the nature of their interactions.

Propranolol introduced by a cut-end method into atrial trabeculae evoked negative inotropic response without any significant changes in basic electrical parameters. This effect was resistant to noradrenaline but not to dibutyryl cAMP. These results suggest that existence of intracellular beta adrenoreceptors involved in the control of the contraction.