Recent advances in cell-based in vitro models for predicting drug permeability across brain, intestinal, and pulmonary barriers

ABSTRACT

Introduction

Recent years have witnessed remarkable progress in the development of cell-based in vitro models aimed at predicting drug permeability, particularly focusing on replicating the barrier properties of the blood-brain barrier (BBB), intestinal epithelium, and lung epithelium.

Area covered

This review provides an overview of 2D in vitro platforms, including monocultures and co-culture systems, highlighting their respective advantages and limitations. Additionally, it discusses tools and techniques utilized to overcome these limitations, paving the way for more accurate predictions of drug permeability. Furthermore, this review delves into emerging technologies, particularly microphysiological systems (MPS), encompassing static platforms such as organoids and dynamic platforms like microfluidic devices. Literature searches were performed using PubMed and Google Scholar. We focus on key terms such as in vitro permeability models, MPS, organoids, intestine, BBB, and lungs.

Expert Opinion

The potential of these MPS to mimic physiological conditions more closely offers promising avenues for drug permeability assessment. However, transitioning these advanced models from bench to industry requires rigorous validation against regulatory standards. Thus, there is a pressing need to validate MPS to industry and regulatory agency standards to exploit their potential in drug permeability prediction fully. This review underscores the importance of such validation processes to facilitate the translation of these innovative technologies into routine pharmaceutical practice.

KEYWORDS:

• Absorption
• blood-brain barrier
• microfluidic systems
• organoids
• tight junction
• transepithelial electrical resistance
• in vitro-in vivo extrapolation
• IVIVE

Article highlights

• Two-dimensional in vitro models are simple and cost-effective enabling high-throughput screening of permeability to predict drug absorption during the early stages of drug development.

• Microphysiological systems provide a closer representation of in vivo conditions than traditional cell cultures by mimicking the complex architecture and cellular interactions of the lung, blood-brain-barrier, and gut epithelium.

• Utilizing these advanced models for permeability studies could accelerate the drug development process by better predicting drug absorption and transport across barriers, which could improve the identification of potential candidates by mitigating late-stage failures and reducing costs and time-to-market for new therapeutics.

• Microphysiological systems offer customizable models for a more precise investigation of permeability and drug responses across different epithelial barriers representative of healthy and disease conditions.

• Moving forward, research focusing on validation and scaling up Microphysiological systems for high-throughput permeability screening will facilitate broader applications in drug discovery and personalized medicine.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was partially funded by a contract with the Food and Drug Administration (75F40122C00182)