A thermoplastic microfluidic platform with integrated electrospun scaffolds for assessing brain cell-specific drug selectivity

Abstract

A major challenge in pharmacology is the limited selectivity of therapeutic compounds toward specific tissues or cells. Drugs often distribute systemically before reaching the intended site of action, affecting nontarget cells and potentially reducing efficacy or causing side effects. Traditional two-dimensional cultures fail to reproduce the three-dimensional architecture and dynamic microenvironment of tissues. Here, we present a novel microfluidic platform integrating an electrospun scaffold to assess the selective interaction of drugs or nanosystems with different central nervous system (CNS) cell types as model. The device was engineered to enable the coculture of two distinct cell types in separated compartments that remain fluidically connected, thus simulating physiological exposure and transport conditions. This setup allows for dynamic testing of compound selectivity in a more relevant context. Overall, this integrated and modular system represents a promising tool for advancing in vitro brain models and improving the predictive power of preclinical drug screening strategies targeting the CNS.