A Versatile Human Intestinal Organoid-Derived Epithelial Monolayer Model for the Study of Enteric Pathogens

While traditional laboratory techniques and animal models have provided valuable knowledge in discerning virulence mechanisms of enteric pathogens, the complexity of the human gastrointestinal tract has hindered our understanding of physiologically relevant, human-specific interactions and, thus, has significantly delayed successful vaccine development. The human intestinal organoid-derived epithelial monolayer (HIODEM) model closely recapitulates the diverse cell populations of the intestine, allowing for the study of human-specific infections.

Three-Dimensional Tumor Spheroids as a Tool for Reliable Investigation of Combined Gold Nanoparticle and Docetaxel Treatment

Radiotherapy and chemotherapy are the gold standard for treating patients with cancer in the clinic but, despite modern advances, are limited by normal tissue toxicity. The use of nanomaterials, such as gold nanoparticles (GNPs), to improve radiosensitivity and act as drug delivery systems can mitigate toxicity while increasing deposited tumor dose. To expedite a quicker clinical translation, three-dimensional (3D) tumor spheroid models that can better approximate the tumor environment compared to a two-dimensional (2D) monolayer model have been used. We tested the uptake of 15 nm GNPs and 50 nm GNPs on a monolayer and on spheroids of two cancer cell lines, CAL-27 and HeLa, to evaluate the differences between a 2D and 3D model in similar conditions. The anticancer drug docetaxel (DTX) which can act as a radiosensitizer, was also utilized, informing future potential of GNP-mediated combined therapeutics. In the 2D monolayer model, the addition of DTX induced a small, non-significant increase of uptake of GNPs of between 13% and 24%, while in the 3D spheroid model, DTX increased uptake by between 47% and 186%, with CAL-27 having a much larger increase relative to HeLa. Further, the depth of penetration of 15 nm GNPs over 50 nm GNPs increased by 33% for CAL-27 spheroids and 17% for HeLa spheroids. These results highlight the necessity to optimize GNP treatment conditions in a more realistic tumor-life environment. A 3D spheroid model can capture important details, such as different packing densities from different cancer cell lines, which are absent from a simple 2D monolayer model.

Making Concentrated Pterostilbene Highly Bioavailable in Pressure Processed Phospholipid Nanoemulsion

Pterostilbene, a dimethylether analog of resveratrol, has been found to have potent biological activity. However, the bioavailability of pterostilbene in the biological system is limited due to its poor solubility in an aqueous environment. A nanoemulsion system was designed for this purpose. Lecithin-based nanoemulsion was formed after 3 cycles through a high-pressure homogenizer at 500 psi. The rheological properties and particle size were measured using dynamic light scattering and a viscometer. The storage stabilities of the prepared formulation were determined based on its ability to maintain its particle size and loading concentration. According to the experimental results, the lecithin-based nanoemulsion system contained approximately 9.5% of pterostilbene. Over the 28-day stability test, the particle size, zeta potential, and encapsulation of pterostilbene in the nanoemulsion did not change significantly, indicating good storage stability. The positive effect of the prepared nanoemulsion system on bioavailability was studied and confirmed using in vitro lipolysis and a caco-2 monolayer model.