ISHC2015

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.