(760f) The Influence of Fluid Dynamics on Nanomaterial Delivery Efficiency: Elucidating the Roles of Particle Size and Cell Model

Colloidal silver nanoparticles (AgNPs) are being increasingly utilized in biomedical applications, such as drug/gene delivery and bio-imaging techniques. However, the effectiveness of these procedures are highly dependent upon sustained, strong interactions between AgNPs and the surrounding environment; referred to as the nano-bio interface. Therefore, prior to the development of effective NP-based therapeutics, a reliable and accurate means of assessing NP delivery must be established. Both in vitro and in vivo methodologies are currently being utilized for evaluation, however, limited correlation exists between these models due to their fundamental differences. One way to overcome this limitation is through the development of enhanced in vitro environments that retain the advantages of cellular systems but more accurately mimic true physiology. For example, the introduction of fluid dynamics into a cellular system can impact particokinetics, the composition of the nano-bio interface, and the subsequent cellular response.

In the work presented here, a dynamic in vitro environment was successfully utilized to characterize the AgNP deposition efficiency. Dynamic flow was generated through the use of a peristaltic pump, operating at a flowrate to produce a linear tube velocity of 0.2 cm/s: equivalent to know capillary rates. To better understand how dynamic flow impacted deposition, two experimental cell models were utilized; an adherent lung epithelial model (A549) and a suspension monocyte model (U937). Additionally, as bio-transport mechanisms are a function of particle size we included two experimental, citrate-coated AgNPs – 5 and 50 nm.

The AgNPs were introduced into both cell models and incubated for 24 hours under either static or dynamic conditions. After this exposure, the AgNP deposition was evaluated and found to vary as a function of flow environment, cell model, and primary particle size. As expected, dynamic flow significantly decreased the delivered dose of AgNPs to the adherent lung cells; with the 5 nm AgNPs experiencing the greatest drop in deposition. However, AgNP delivery was increased within a dynamic environment for the monocytes, due to increased nano-cellular interactions. While an increase in deposition was seen for both the 5 and 50 nm particles, the 5 nm AgNPs were associated with a greater increase, roughly 20%. For both cell models, the subsequent cytotoxicity, stress, and inflammatory responses correlated to delivered NP dosages. Specifically, reactive oxygen species (ROS) and p53 levels were used to assess cellular stress and the secretion of pro-inflammatory cytokines were the selected marker for inflammatory activation. This work highlights the need for NP deposition, safety, and efficacy evaluations to be carried out in a physiologically relevant system, as environmental variables are capable of influencing NM properties, behaviors, and downstream bioeffects.