Development of new approaches for treatment of
invasive fungal infections encompasses new delivery systems for approved and investigational compounds, as well as exploiting the cell membrane, cell wall and
virulence factors as putative antifungal targets. Novel delivery systems consisting of
cyclodextrins, cochleates, nanoparticles/
nanospheres and long circulating ('stealth')
liposomes, substantially modulate the pharmacokinetics of existing compounds, and may also be useful to enhance the delivery of
antifungal agents to sites of
infection. Further insights into the structure-activity relationship of the antifungal
triazoles that target the biosynthesis of
ergosterol in the fungal cell membrane have led to the development of highly potent broad spectrum agents, including
posaconazole,
ravuconazole and
voriconazole. Similarly, a novel generation of cell-wall active semisynthetic
echinocandin 1,3
beta-glucan inhibitors (
caspofungin,
FK463, and VER-002) has entered clinical development. These agents have potent and broad-spectrum activity against Candida spp, and potentially useful activity against Aspergillus spp. and Pneumocystis carinii. The ongoing convergence of the fields of molecular pathogenesis, antifungal pharmacology and
vaccine development will afford the opportunity to develop novel targets to
complement the existing antifungal armamentarium.