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Purpose: We present a heterocyclic-based drug delivery platform that optimizes the concentration of a systemic drug at a location of interest. As a therapeutic proof of concept, we apply the system to the construction of an antibiotic agent based on vancomycin.
Background: Our prior studies have shown that an area of the body pre-implanted with a biomaterial containing a bioorthogonal reaction partner (trans-cyclooctene, TCO) can increase by ten times the local concentration of a heterocycle (tetrazine, Tz) carrying a radioactive payload in-vivo. Now we present a platform that localizes and releases small molecules at the desired location (Fig. 1).
Methods/Results: We modified fluorophores and vancomycin with TCO and as well as synthesized an alginate biomaterial modified with tetrazine (Tz-gel). We tested them through in-vivo and in-vitro models over multiple days. The results indicate that the “Catch & Release” method can deliver an increased payload to a local area pre-implantated with the biomaterial. The in-vitro therapeutic efficacy of the releasable vancomycin was comparable to vancomycin when tested in the presence of the Tz-gel against luminescent methicillin sensitive Staph. aureus (MSSA, Xen 29, Perkin Elmer, MA).Conclusions: We present a drug delivery system that enables medical practitioners to direct drug to specific locations of the body by pre-implanting a biomaterial. This system could have major implications to improve the therapeutic index of new and old drugs.