Covalent microparticle-drug conjugates for biological targeting
First Claim
1. A composition of matter comprising a biologically-active compound that is an antimicrobial drug, a microparticle, and a cleavable linker moiety comprising two linker functional groups, wherein the cleavable linker moiety has a first end and a second end and wherein the microparticle is attached to the first end of the linker moiety through a first linker functional group and the biologically-active compound is attached to the second end of the linker moiety through a second linker functional group, and wherein the cleavable linker moiety is specifically cleaved inside a phagocytic mammalian cell infected with a microorganism.
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Abstract
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 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 an organic linker molecule which is the target of a microorganism-specific protein having enzymatic activity. Thus, the invention provides cell targeting of drugs wherein the targeted drug is only released 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 an organic 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 antimicrobial drugs and agents wherein the surface or outside extent of the microparticle is covered with a degradable coating that is specifically degraded within an infected phagocytic mammalian cell. Methods of inhibiting, attenuating, arresting, combatting and overcoming microbial infection of phagocytic mammalian cells in vivo and in vitro are also provided.
178 Citations
15 Claims
- 1. A composition of matter comprising a biologically-active compound that is an antimicrobial drug, a microparticle, and a cleavable linker moiety comprising two linker functional groups, wherein the cleavable linker moiety has a first end and a second end and wherein the microparticle is attached to the first end of the linker moiety through a first linker functional group and the biologically-active compound is attached to the second end of the linker moiety through a second linker functional group, and wherein the cleavable linker moiety is specifically cleaved inside a phagocytic mammalian cell infected with a microorganism.
Specification