# Steering the Clinical Translation of Delivery Systems for Drugs and Health Products
## 3 Poster Presentations
### Developing a 3-Compartment Eye Flow Cell for Pre-Clinical Investigation  
[PERSON] *, [PERSON], [PERSON] and [PERSON]  
Department of Drug Science and Technology, University of Torino, 10125 Torino, Italy  
* Correspondence: [EMAIL_ADDRESS]  
Pre-clinical pharmacologic studies for new preparations, aimed to investigate the mode of action, the effects, as well as ocular safety and pharmacokinetics of drugs and devices, have been so far dominated by the use of animal models. Despite their importance, presently many efforts are underway to reduce the number of animals used in testing, both to comply with ethical concerns and to reduce costs and time. Other findings of animal testing are the differences between animals and humans, the possible formation of antidrug antibodies and the variability of the experimental techniques used for each species.  
In vitro models can offer a valid alternative to animal studies; among these, several have been established in the past few years to mimic different parts of the ocular system; anyway, little has been reported about in vitro model that accounts for the aqueous perfusion flow.  
To address this gap, starting from the literature [84], we engineered a Plexiglas 3-compartment eye flow cell (Figure 23), mimicking the anterior and the posterior cavities of the eye. In addition, a semipermeable disk is placed vertically between the posterior section and a retro-retinal hollow unit that can be used as a support for retinal cell cultures to mimic the blood retinal barrier. An injection port is placed at the top of the vitreous cavity, while an aqueous inlet port connected to a dispensing pump, ensuring a perfusion flow rate of 2.0 \(\upmu\)L/min, is placed in the vitreous cavity near the membrane barrier and an outlet port is placed in the anterior cavity to mimic the aqueous outflow in humans. The cell is filled with simulated vitreous (0.2% w/w agar/0.25% w/w hyaluronic acid).  
Preliminary experiments were performed on dyes solutions to validate the model and then on (i) eefuroxime-loaded nanocomposite thermoreversible hydrogel and (ii) Avastin(r) solution. In all experiment's samples were injected into the posterior cavity while, at scheduled times, samples were collected from the anterior outlet port and then analyzed by HPLC to evaluate the concentration.  
Although the model is still in an experimental stage, preliminary data showed this model to be a promising tool to obtain pre-clinical information about novel ophthalmic preparation namely to predict (1) dissolution/distribution (2) release profile and (3) clearance from the vitreous cavity of the candidate drug.  
Further efforts must be focused towards providing this ocular cell with a posterior disk impregnated with Adult Retinal Pigment Epithelial cells (ARPE-19) mimicking the retinal pigment epithelium to create a more robust and effective cell-based platform for ophthalmic research.  
**Acknowledgments:** This research was funded by Fondazione CRT-grant RF 2017.0820 and co-funded by MIUR, University of Turin-Fondi Ricerca Locale (ex-60%).  
Figure 23: Ocular flow cell: (**a**) the three-compartments unit secured with four screws; (**b**) the red-circled semipermeable disk, possible support for retinal cells.