442814 Remotely Activated Biomaterials for Use in Optimizing Localized Cancer Therapy

Monday, November 9, 2015
Exhibit Hall 1 (Salt Palace Convention Center)
Tanner Barnes1, Anita Tolouei2, Rosa Ghatee1, Robert Blease1, Tania Emi2 and Stephen Kennedy3, (1)Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, RI, (2)Chemical Engineering, University of Rhode Island, Kingston, RI, (3)Electrical, Computer, and Biomedical Engineering and Department of Chemical Engineering, University of Rhode Island, Kingston, RI

Remotely activated biomaterials for use in optimizing localized cancer therapy 

Barnes, T.1, Tolouei, A.2, Ghatee, R.1, Blease, R.1, Tania, E.2, Kennedy, S.1, 2

1Department of Electrical, Computer, and Biomedical Engineering

2 Department of Chemical Engineering, University of Rhode Island, Kingston, RI


Advances in medical technology have greatly increased the 5-year survival rate for many types of cancer; however, there is still a need for improved therapies. Many current treatments involve the systemic delivery of cytotoxins. A problem with systemic drug delivery is that much higher concentrations of drug must be administered to ensure therapeutic concentrations are present at the target site. An alternative to systemic delivery is to implant a drug-laden biomaterial at the target site, which can sustain a localized therapeutic concentration and minimize off-target side effects. While promising, most current biomaterials rely on diffusive or degradation-based release, which yields relatively constant delivery profiles over time (which are not necessarily optimal). We propose a responsive biomaterials approach utilizing electrically responsive gels (7 wt % poly(acrylic acid) cross-linked with 1 wt % polyethylene glycol dimethacrylate (PEG-DM)), magnetically responsive gels (1 wt % alginate with 7 wt % Fe3O4 cross-linked with 2.5 mM adipic acid dihydrazide), and ultrasonically responsive gels (1 wt % alginate ionically cross-linked with 2.5 CaSO4). These hydrogels’ abilities to deliver drugs in response to remotely applied stimuli enable the on-demand control required for clinicians to alter the course of therapies according to patient specifics and/or up-to-date diagnostics and prognoses. Additionally, we have shown these responsive hydrogels to be capable of delivering chemotherapeutics with more nuanced delivery profiles versus time, including the ability to provide pulsatile mitoxantrone delivery profiles. We also determined that these pulsatile mitoxantrone delivery profiles resulted in lower B16-F10 mouse melanoma cancer cell survival when compared to controls and other non-pulsatile delivery profiles. Moreover, pulsatile profiles could be optimized to dramatically reduce B16-F10 survival after three days of treatment and impede B16-F10 recovery after one day post-treatment (optimized pulsatile regiment: 2 hour mitoxantrone pulses at 24 μg/ml every 24 hours for 3 days). These findings suggest that electrically, magnetically, and ultrasonically responsive biomaterials may be useful tools for improving chemotherapeutic strategies by being able to deliver optimized chemotherapeutic profiles over time directly at tumor sites.

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