Brain distribution study of [C]-Riluzole following intranasal administration in mice.

Amyotrophic lateral sclerosis (ALS) presents a substantial challenge due to its complex nature, limited effective treatment options, and modest benefits from current therapies in slowing disease progression. This study explores the potential of intranasal (IN) delivery to enhance the CNS delivery of riluzole (RLZ), a standard ALS treatment which is subject to blood-brain barrier efflux mechanisms. Additionally, the impact of elacridar (ELC), an efflux pump inhibitor, on IN RLZ CNS bioavailability was examined.

Resident Physicians Have an Increased Risk of Adverse Driving Events Following Extended-Duration Work Shifts: A Systematic Review.

Resident physicians often work extended-duration work shifts (EDWSs) exceeding 16 hours. EDWSs are associated with fatigue, workplace errors, mental health problems, and motor vehicle incidents. A 2019 systematic review reported that resident physicians had an increased risk of motor vehicle collisions (MVCs) and of falling asleep at the wheel after EDWSs.

Polyinosinic/Polycytidylic Lipid Nanoparticles Enhance Immune Cell Infiltration and Improve Survival in the Glioblastoma Mouse Model.

Glioblastoma (GBM) immunotherapy is particularly challenging due to the pro-tumorigenic microenvironment, marked by low levels and inactive immune cells. Toll-like receptor (TLR) agonists have emerged as potent immune adjuvants but failed to show improved outcomes in clinical trials when administered as a monotherapy. We hypothesize that a combined nanoparticulate formulation of TLR agonist and immunogenic cell death-inducing drug (doxorubicin) will synergize to induce improved GBM immunotherapy.

RNA lipid nanoparticles as efficient in vivo CRISPR-Cas9 gene editing tool for therapeutic target validation in glioblastoma cancer stem cells.

In vitro and ex-vivo target identification strategies often fail to predict in vivo efficacy, particularly for glioblastoma (GBM), a highly heterogenous tumor rich in resistant cancer stem cells (GSCs). An in vivo screening tool can improve prediction of therapeutic efficacy by considering the complex tumor microenvironment and the dynamic plasticity of GSCs driving therapy resistance and recurrence. This study proposes lipid nanoparticles (LNPs) as an efficient in vivo CRISPR-Cas9 gene editing tool for target validation in mesenchymal GSCs.