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. Author manuscript; available in PMC: 2022 Feb 10.
Published in final edited form as: J Control Release. 2020 Nov 19;330:284–292. doi: 10.1016/j.jconrel.2020.11.031

Fig. 1. Macrophage-targeted drugamer enables a sustained delivery of ciprofloxacin to alveolar macrophages.

Fig. 1.

Schematic showing the composition polymeric ciprofloxacin prodrug and its mechanism for enhancing alveolar macrophage uptake and intracellular antibiotic release. (1) The drugamer is composed of multivalent mannose ligands that act both as solubilizing agents and targeting residues, thus enhancing drugamer internalization by alveolar macrophages. (2) Drugamer binding to mannose receptors induces receptor-mediated endocytosis. The protease-cleavable dipeptide motif (Valine-Citrulline) linking ciprofloxacin to the polymer backbone is subsequently cleaved by intracellular proteases, such as cathepsins, allowing release of the antibiotic in the alveolar macrophage and killing of intracellular bacteria.