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Monday, August 24 • 3:40pm - 4:00pm
[0087] Catch & Release Drug Delivery System – Heterocycles, Bioorthogonal Chemistry and Implantable Biomaterials Optimize the Pharmacokinetics of Systemic Small Molecules

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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.

ST Lecturers
avatar for Jose M. Mejia Oneto

Jose M. Mejia Oneto

Founder, Shasqi
Orthopaedic Surgery ResidentDrug DeliveryAntibioticsChemotherapy

Monday August 24, 2015 3:40pm - 4:00pm PDT
MCC Theater