This invention provides novel methods and reagents for specifically delivering biologically active compounds to phagocytic mammalian cells. The invention also relates to specific uptake of such biologically active compounds by phagocytic cells and delivery of such compounds to specific sites intracellularly. The invention specifically relates to methods of facilitating the entry of antiviral and
antimicrobial drugs and other agents into phagocytic cells and for targeting such compounds to specific organelles within the
cell. The invention specifically provides compositions of matter and pharmaceutical embodiments of such compositions comprising conjugates of such
antimicrobial drugs and agents covalently linked to particulate carriers generally termed microparticles. In particular embodiments, the
antimicrobial drug is covalently linked to a
microparticle via a
cleavable linker moiety that is non-specifically cleaved in a
phagocytic cell. In additional embodiments, the biologically-
active compound is provided in an inactive,
prodrug form that is activated by a chemical or enzymatic activity specific for cells infected by a
microorganism, particularly a
pathological or
disease-causing
microorganism. Thus, the invention provides
cell targeting of drugs wherein the targeted
drug is only activated in cells infected with a particular
microorganism. Alternative embodiments of such specific
drug delivery compositions also contain polar lipid carrier molecules effective in achieving
intracellular organelle targeting in infected phagocytic mammalian cells. Particular embodiments of such conjugates comprise antimicrobial drugs covalently linked both to a
microparticle via a
cleavable linker molecule and to a polar lipid compound, to facilitate targeting of such drugs to particular subcellular organelles within the
cell. Also provided are porous microparticles impregnated with antiviral and antimicrobial drugs and agents wherein the surface or outside extent of the
microparticle is covered with a degradable
coating that is degraded within a phagocytic
mammalian cell. Also provided are nonporous microparticles coated with an antiviral or
antimicrobial drug and further coated wherein the surface or outside extent of the microparticle is covered with a degradable
coating that is degraded within a phagocytic
mammalian cell. Methods of inhibiting, attenuating, arresting, combating and overcoming microbial infection of phagocytic mammalian cells
in vivo and
in vitro are also provided.