No abstract

The fungicidal activity of Bacillus subtilis QST713 has been utilized for the highly effective and environmentally safe protection of crops against a variety of pathogens. It is based mainly on the production of cyclic lipopeptides of the fengycin (FEs), surfactin, and iturin families. The mixed population of native FEs forms micelles which solubilize individual FEs such as agrastatin 1 (AS1) that are otherwise rather insoluble on their own. Fluorescence lifetime-based calcein efflux measurements and cryo transmission electron microscopy show that these FEs show a unique scenario of membrane permeabilization. Poor miscibility of FEs with lipid probably promotes the formation of pores in 10% of the vesicles at only≈1μM free FE and in 15% of the vesicles at 10 μM. We explain why this limited, all-or-none leakage could nevertheless account for the killing of virtually all fungi whereas the same extent of graded vesicle leakage may be biologically irrelevant. Then, crystallization of AS1 and micellization of plipastatins cause a cut-off in leakage at 15% that might regulate the biological activity of FEs, protecting Bacillus and plant membranes. The fact that FE micelles solubilize only about 10 mol-% fluid lipid resembles the behavior of detergent resistance.

The identification of novel drug candidates for the treatment of diseases like cancer, infectious diseases, or allergies (especially asthma) assigns new tasks for pharmaceutical technology. With respect to drug delivery several problems occur such as low solubility and hence low bioavailability or restriction to inconvenient routes of administration. Nanotechnological approaches promise to circumvent some of these problems, therefore being well suited for future applications as nanomedicines. Furthermore, efficient and sufficient loading is a critical issue that is approached through mesoporous particles and/or through nonspherical particles both offering larger volumes and surfaces. Special interest is laid on the effect of shape of particulate materials on the body and related physiological mechanisms. The modified response of biological systems on different shapes opens a new dimension to adjust particle system interaction. Finally, the biological response to these systems will determine the fate with respect to their therapeutic value. Therefore, the interaction pattern between nonspherical particulate materials and biological systems as well as the production processes are highlighted.

CitationMacrophage uptake of cylindrical microparticles investigated with correlative microscopy. 2015, 95 (Pt A):151-5 Eur J Pharm Biopharm