Interdisciplinary Training

Carol O'Hear

"Antibody Buffering: A Novel Mechanism for Drug Delivery"

When drugs are administered clinically, a much higher dose than the minimum therapeutic concentration is given in order to combat drug elimination and keep the drug at the target site for a long period of time.  In many instances, the result of the excess drug is increased toxicity to the body and proportionally faster elimination.  

We propose a new paradigm for drug delivery.  "Antibody buffering" describes the concept that administration of a drug with a drug-specific antibody will keep a stable, bioavailable concentration of the drug in the body for a longer period of time, and with less toxic side effects, than if the drug were administered on its own.  This concept is well-suited to the delivery of unstable or rapidly eliminated drugs, insoluble drugs, and therapeutic peptides and proteins.  

We aim to develop and test antibody buffering of a common anti-cancer drug. Antibodies will be raised to the DNA topoisomerase I inhibitor topotecan.  They will be used in pharmacokinetic experiments in a rat model to determine the efficacy of the antibody to buffer this drug.  Also, a previously characterized murine anti-lysozyme antibody will be used in rat pharmacokinetic experiments as a model of antibody buffering of systematically-administered proteins.  These experiments will serve as proof-of-principle as to whether antibody buffering can be further developed for use in clinical practice.