Authors:

Laine Chapman

Date Created:

Not specified

Course Title:

Professor:

Not specified

About Paper:

Intrathecal injection of nanoparticle-based therapeutics involves the administration of encapsulated substances into the cerebrospinal fluid (CSF) contained within the subarachnoid space surrounding the spinal cord. This method of drug delivery enables a higher concentration of therapeutic agent to be delivered within the central nervous system while minimizing off-target exposure and toxicity. While these findings are promising, recent biodistribution studies indicate that most nanocarriers remain confined to the leptomeninges after intrathecal injection and fail to reach deeper neural tissues, suggesting the presence of molecular transport barriers within the tissues lining the subarachnoid space. Recent studies have also indicated that nanoparticle interactions with extracellular matrix proteins (ECM) can negatively impact their transport in a tissue-specific manner. However, 1) the specific ECM proteins involved in nanoparticle-ECM interactions after intrathecal injection and 2) the impact of these binding interactions on nanoparticle transport are poorly understood. The chosen research approach aided in building and refining a microfluidic model of the subarachnoid space to study how the ECM of surrounding tissues affects nanoparticle transport and retention. We tested new microfluidic design features under inverted flow conditions and identified nanoparticle binding partners in the ECM using proteomics. Altogether, these in vitro intrathecal delivery models can be used to investigate the impact of nanoparticle-ECM binding interactions on bulk transport in CSF. Keywords: Intrathecal; Injection; Nanoparticles; CSF

Source:

Purdue University / 2025

Topics:

No topics listed

Co-authors:

Laine Chapman