"Using Molecular Interactions to Control Release Rate and Refilling of Drug Delivery Devices"

Horst von Recum, PhD
Department of Biomedical Engineering
Case Western Reserve University
Cleveland, OH

Controlled delivery of molecules has found its way into all walks of life from dishwasher detergent, to biomedical devices, to paint.   In biomedical applications controlled drug delivery is used to provide appropriate dosing of therapeutics to meet physiological need.  For local drug delivery this also includes optimizing effects at the needed site, while bypassing some or all of the detrimental effects of systemic delivery.  One of the major factors that researchers in this field have to work with is Fick’s First Law of Diffusion, namely that drug will follow a concentration gradient, which results in extremely rapid release in early time points followed by a longer period of much slower release.  Often times this bi-phasic release is not sufficient to address the biomedical problem, leaving the investigator only limited capacity for adjustment of polymer properties to modify the Diffusivity term of Fick’s Law.  The von Recum lab has been exploring the use of intentionally designed molecular interactions to add additional factors controlling the rate of drug release, namely adding a specific affinity between drug and polymer, making this interaction become the rate limiting step.  This research field, termed “affinity-based drug delivery” is capable of reducing the burst phase and prolonging release from hours to days to months.  In addition, such controlled delivery devices, once empty still maintain their molecular pockets, which can be refilled for additional therapeutic windows, and periods of delivery.  In this work we will show applications ranging from device infection, cancer therapy, cardiovascular restenosis, and stem cell homing and proliferation in tissue engineering and regenerative medicine.  Further we will show how such devices are capable of being refilled in vivo and demonstrate additional therapeutic windows.  In closing we feel that the prolonged release, and refilling capacity of affinity-based drug delivery devices will open new fields of application previously not addressable by devices controlled by diffusion alone.