Organ-on-a-Chip systems for new drugs development.

Ronny Vargas,Andrea Egurbide,Laura Medina

doi:10.5599/admet.942

Ronny Vargas, Andrea Egurbide + Show 1 more

Open Access

https://doi.org/10.5599/admet.942

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Abstract

Research on alternatives to the use of animal models and cell cultures has led to the creation of organ-on-a-chip systems, in which organs and their physiological reactions to the presence of external stimuli are simulated. These systems could even replace the use of human beings as subjects for the study of drugs in clinical phases and have an impact on personalized therapies. Organ-on-a-chip technology present higher potential than traditional cell cultures for an appropriate prediction of functional impairments, appearance of adverse effects, the pharmacokinetic and toxicological profile and the efficacy of a drug. This potential is given by the possibility of placing different cell lines in a three-dimensional-arranged polymer piece and simulating and controlling specific conditions. Thus, the normal functioning of an organ, tissue, barrier, or physiological phenomenon can be simulated, as well as the interrelation between different systems. Furthermore, this alternative allows the study of physiological and pathophysiological processes. Its design combines different disciplines such as materials engineering, cell cultures, microfluidics and physiology, among others. This work presents the main considerations of OoC systems, the materials, methods and cell lines used for their design, and the conditions required for their proper functioning. Examples of applications and main challenges for the development of more robust systems are shown. This non-systematic review is intended to be a reference framework that facilitates research focused on the development of new OoC systems, as well as their use as alternatives in pharmacological, pharmacokinetic and toxicological studies.

Highlights

The development of new drugs is an expensive process that presents several challenges in preclinical and clinical studies [1,2], where a 59 % of the medicines that initiate a clinical study go into phase II, just a 21 % starts phase III, and merely a 10 % reach approval by the regulatory authority
The appearance of adverse effects is one of the main reasons for drug failure, becoming one of the biggest challenges and weaknesses presented by preclinical models as predictors of clinical performance [2,3,4,5]
Liver-on-a-chip models associated with other tissues or organs, such as the intestine, may allow to obtain first-step metabolism profiles closer to those that could be acquired through traditional cell cultures [1,3,89]

Summary

Introduction

The development of new drugs is an expensive process that presents several challenges in preclinical and clinical studies [1,2], where a 59 % of the medicines that initiate a clinical study go into phase II, just a 21 % starts phase III, and merely a 10 % reach approval by the regulatory authority. OoC have the potential to reduce and supplement the use of animals, cell models, and even humans in new drugs development [7]. The design of OoC involves reverse engineering of living organs [42,52], which requires an in-depth study of the organs and their functions to develop systems more physiologically relevant than current in vitro models.

Results

Conclusion