“Tuning Nanoparticles for Ultrasonically Triggered Delivery from Implantable Biomaterials”

AIChE 2015 Annual Student Conference Abstract

November 9^th, 2015

“Tuning nanoparticles for ultrasonically triggered delivery from implantable biomaterials”

Robert Blease¹, Molly Card², Michael Desmarais², Katelyn Ludemann²,

 Tanner Barnes¹, Iftheker Khan², Vinka Craver³, Geoffrey Bothun²,

Stephen Kennedy^1,2

¹Department of Electrical, Computer, and Biomedical Engineering, ²Department of Chemical Engineering, ³Department of Civil and Environmental Engineering,

University of Rhode Island, Kingston RI 02881

In a wide range of biomedical applications—including, but not limited to tissue engineering and cancer therapy—it is highly desirable to coordinate the timing and sequence of multiple therapeutic payloads.  Hydrogel-based biomaterials provide implantable systems for locally delivering therapeutic payloads in tissue engineering and cancer therapy applications. However, most hydrogel-based delivery systems do not provide explicit control over the timing and sequence of multiple payload deliveries.  It has recently been shown that ultrasonically responsive hydrogels provide a means to remotely trigger the delivery of nanoparticle payloads.  We hypothesized that these ultrasonically responsive hydrogels could be used to remotely coordinate the timing and sequence of multiple payloads if the nanoparticles were tuned to have different retention and ultrasonically stimulated release characteristics from the hydrogel.  We therefore aimed to create gold nanoparticles of various sizes and charges and characterize their retention and ultrasonically stimulated release from Ca²⁺ cross-linked alginate hydrogels. Gold nanoparticles (AuNPs) were created using a modified Turkevich method, in which the amount of citrate was altered to modify particle diameter: “small” and “large” particles were measured to be 21.7 ± 0.14 nm and 38.5 ± 0.14 nm, respectively.  AuNPs were decorated with different PEG groups in order to vary the charge. Surface potentials were measured at -21.4mV and -17.6 mV for “negative” small and large particles, respectively and at  -10.7mV and -12.9mV for “neutral” small and large particles, respectively. Hydrogels (1 wt % alginate with 2.5 mM CaSO₄) were cast with AuNPs (~2.5 x 10¹⁷ AuNPs per gel) of various size and charge and placed into vials with 1 mL of phosphate buffer solution (PBS) with Ca²⁺ and Mg²⁺. Nanoparticle release from the hydrogels was measured over a 7-day period. Gels were ultrasonically stimulated on day 7 in order to study the triggered release of AuNPs using a 3–mm sonication probe for either 2 or 5 minutes at an amplitude of only 20% in order to minimize mechanical damage to the hydrogel during sonication. It was found that the small particles diffused faster than the large particles (p < 0.005). Negative particles diffused faster than the neutral particles (p < 0.005). It was also found that sonication increased the rate of release of all particle types (by 2- to 4-fold).  These particles were found not to be cytotoxic in the doses released by the gel. Moving forward, the differences in stimulated and unstimulated release rates observed here should provide an avenue to independently control the delivery profile of multiple drugs attached to the particles in a single implanted gel.