(720a) Invited Talk: Micro- and Nano-Particles for Sustained-Release Therapeutic Drug Delivery

Polymeric particles are highly advantageous for drug delivery because they address limitations with bioavailability, solubility, absorption, and half-life, which currently limit drug efficacy. Unfortunately, the clinical translation of these technologies is extremely challenging. We hypothesize that we can overcome these challenges by investigating the mechanisms that promote cell uptake and retention, particularly in epithelial cells. For this work, we have used both 2D and 3D endometrial cancer models and measured the uptake and retention of rhodamine B-loaded poly(caprolactone) particles. We have shown differences in uptake that are cell-line dependent, and we have also shown differences in responses to paclitaxel, a powerful chemotherapeutic, between the 2D and the 3D models. We have also conducted significant physicochemical characterization on these particles to correlate size and surface properties with uptake and retention and inform future particle designs. Endometrial cancer treatment is of particular interest because endometrial cancer is the sixth most common cancer in women worldwide and is the most common cancer of female reproductive organs, with a rising incidence rate of 1.3% from 2007-2016. Less than ten drugs have been FDA-approved specifically for endometrial cancer treatment. The minuscule amount of effective treatment options, as well as an increase in incidence, shows the need for creating improved treatments for endometrial cancer. Importantly, although these particles are tested in an endometrial cancer model, the findings on epithelial cell uptake and retention are informative for other epithelial cell delivery.