(9e) A Microfluidic Model to Assess Subcutaneous Transport and Pharmacokinetics in Vitro

Subcutaneous injections are one of the most common routes of medication administration and they offer higher patient adherence and the benefit of self-administration compared to intravenous injection. Estimating the bioavailability via the subcutaneous route is thus an essential component of drug development. However, the in vivo estimation of such pharmacokinetics in a pre-clinical setting is far from reliable due to injection site-to-site variations and poor correlation between human and animal data. An ideal in vitro model can address these issues using a properly controlled microenvironment that is physiologically relevant. Nevertheless, such models are not currently available and those that are available are void of critical cellular components. In this talk, we introduce a microfluidics-based approach to mimicking the subcutaneous physiology and eventually evaluating pharmacokinetics.

Our microfluidic device incorporates critical elements of the subcutaneous space including multiple relevant cell types and vascular flow. Transport properties measured in this device can be translated to pharmacokinetics obtained from in vivo studies. We validated that the measured diffusivities in our device are on the same order of magnitude as those measured in vivo. We were able to capture the effects of molecular weight, shape and charge on the rate of subcutaneous diffusion. By changing cell types, we also compared data between human and mice subcutaneous environment. Our device demonstrates the potential of cellular microfluidic devices as a controlled and predictable means for studying drug transport in the subcutaneous space.