BE Seminar: Drug Delivery across Biological Barriers for combatting and preventing infectious diseases

Title: Drug Delivery across Biological Barriers for combatting and preventing infectious diseases.

Prof. Dr. Claus-Michael Lehr

Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI) Dept of Drug Delivery. and

Saarland University, Dept of Pharmacy,

Saarbrücken, Germany.

Abstract: Urgently needed anti-infective drugs and vaccines must reach their targets safely and efficiently. Not only the body’s outer epithelia, like e.g., gut, skin and lung, but also the bacterial cell envelope as well as the polymer matrix of bacterial biofilms represent important biological barriers which may delimit the transport of anti-infectives to their site of action (“bacterial bioavailability”).

To model the air-blood barrier of the peripheral human lung, our group was the first who published a protocol for growing monolayers of human alveolar epithelial cells in primary culture (hAEpC) to develop functional tight junctions and high transepithelial electrical resistance (TEER). Later we introduced a first polyclonal human alveolar epithelial (hAELVi) and just recently a monoclonal cell line (Arlo) with similar properties. These epithelial cells may be implemented in various micro-physiological systems, also to study the effect of breathing and co-cultivated with other cells types, like e.g., macrophages or endothelial cells. A particular challenge is the mixed culture with bacterial biofilms to model chronic lung infections, which can meanwhile be realized most elegantly by 3D bioprinting.

Such complex in-vitro models aim to reflect the (patho)physiology of specific organs or tissues either in healthy or reduce diseased state and to generate clinically meaningful readouts. They have been used for developing novel anti-infectives, like e.g., quorum sensing inhibitors, aiming to eradicate pathogens without inducing antimicrobial resistance. Aerosolizable nano-antibiotics are also being investigated to combat intracellular infections, such as e.g., tuberculosis or viral infections by Crispr/CAS-like approaches.

About The Speaker: Claus-Michael Lehr is Professor at Saarland University as well as cofounder and head of the department “Drug Delivery and Biological Barriers” at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), which was established as a branch of the Helmholtz Centre for Infection Research (HZI) Braunschweig in 2009. Prof. Lehr has also been cofounder of Across Barriers GmbH and of PharmBioTec GmbH, a non-for-profit contract research organization.

The research theme of Professor Lehr’s team is (preferentially: non-invasive) drug delivery across biological barriers, in particular the epithelia of the gastrointestinal tract, the skin, and the lungs. Recently, this has been expanded to microbial barriers, such as the bacterial cellular envelope, biofilms and host cell membranes. A substantial part of the lab’s activities is dedicated to innovative carrier’s systems, often based on nanotechnology, capable of safely and efficiently delivering drugs and vaccines across these barriers. In this context, the lab systematically investigates predictive cells and tissue models, preferentially human-based, to evaluate the safety and efficacy of novel therapeutic concepts and to facilitate their translation into the clinic.