Drug delivery systems for delivering agents capable of reducing the quantity of residual
antibiotics reaching the colon following oral or parenteral
antibiotic therapy, and for delivering metallo-dependent enzymes, and methods of using the
drug delivery systems, are disclosed. The
drug delivery systems include
pectin beads that encapsulate the
active agent (which can be a metallo-dependent
enzyme), where the
pectin is crosslinked with
zinc or any
divalent cation of interest and the
pectin beads are coated with Eudragit®-type polymers. The
drug delivery systems are orally administrable, but can deliver the active agents to the colon. In some embodiments, they can administer the agents to various positions in the
gastro-intestinal tract, including the colon. One metallo-dependent
enzyme is the β-lactamase L1 from
Stenotrophomonas maltophilia, and agents that inactivate macrolide,
quinolone, fluoroquinolone or
glycopeptide antibiotics can also be used. The delivery of the
active agent can be modulated to occur at various pre-selected sites of delivery within the intestinal tract by gelling / crosslinking a mixture of the
active agent, such as a metallo-dependent
enzyme, and pectin, with
divalent metallic cations such as Ca+2 or Zn+2. A stable metallo-dependent enzyme formulation can be delivered to the lower intestine or colon. The use of
zinc cations to crosslink the pectin is particularly preferred when specific metallo-dependent enzymes, which are Zn2+ dependent, could interact with other cationic species if they were used to gel the pectin beads and thus adversely affect the activity of such metallo-dependent enzymes.