The formulation of therapeutic proteins such as Brain-Derived Neurotrophic Factor (BDNF) remains difficult because of their inherent instability and limited bioavailability, especially in central nerv Show more
The formulation of therapeutic proteins such as Brain-Derived Neurotrophic Factor (BDNF) remains difficult because of their inherent instability and limited bioavailability, especially in central nervous system delivery. In this study, we propose an integrated computational-experimental workflow for the rational selection of excipients to optimize BDNF-loaded cubosomal formulations. Structure-based computational analyses-including SiteMap evaluation, molecular docking, and molecular dynamics (MD) simulations-were used to characterize potential binding sites, and assess the molecular compatibility of lipids, stabilizers, and hydrotropes with BDNF. Among the screened excipients, phytantriol showed the most favorable polar and hydrophobic interactions with the protein, while Tween 80 and PEG 200 were identified as the preferred stabilizer and hydrotrope, respectively. The MD trajectories revealed that protein-excipient contacts were transient yet overall stabilizing, helping the protein maintain its conformational integrity under simulated conditions. Experimental confirmation using Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy supported these observations by demonstrating that BDNF's secondary structure was preserved in the presence of the selected excipients. This study provides molecular-level insight into excipient-protein interactions and demonstrates a predictive strategy for guiding the design of stable neurotrophin formulations. Show less
The blood-brain barrier (BBB) presents a critical challenge in treating central nervous system (CNS) disorders, particularly aggressive brain cancers such as glioblastoma (GBM) and medulloblastoma (MB Show more
The blood-brain barrier (BBB) presents a critical challenge in treating central nervous system (CNS) disorders, particularly aggressive brain cancers such as glioblastoma (GBM) and medulloblastoma (MB). RNA therapies exploit endogenous cellular machinery to modulate gene expression, targeting previously undruggable pathways. RNA and CRISPR gene therapies hold transformative potential for brain cancer but demand breakthroughs for enhanced drug transport across the BBB. While clinical achievements in non-CNS diseases validate their efficacy, interdisciplinary collaboration is essential to advance nanoparticles (NPs) engineering, immune evasion, and non-invasive delivery for CNS applications. NPs are indispensable for advancing RNA therapies in brain cancer, with lipid nanoparticles (LNPs) and viral vectors leading clinical translation. Innovations in targeting (e.g., GLUT1, RVG peptide, ApoE mimetic peptide) and non-invasive delivery (e.g., focused ultrasound) are critical to overcome the BBB limitations. This review highlights the different strategies that can be utilized to deliver RNA-based therapies to the brain and summarizes the recent clinical efforts to deliver the RNA. Show less
Type 2 diabetes mellitus (T2DM) is a worldwide health problem that has raised major concerns to the public health community. This chronic condition typically results from the cell's inability to respo Show more
Type 2 diabetes mellitus (T2DM) is a worldwide health problem that has raised major concerns to the public health community. This chronic condition typically results from the cell's inability to respond to normal insulin levels. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the primary incretin hormones secreted from the intestinal tract. While clinical research has extensively explored the therapeutic potential of GLP-1R in addressing various T2DM-related abnormalities, the possibility of GIPR playing an important role in T2DM treatment is still under investigation. Evidence suggests that GIP is involved in the pathophysiology of T2DM. This chapter focuses on examining the role of GIP as a therapeutic molecule in combating T2DM, comparing the past, present, and future scenarios. Our goal is to delve into how GIP may impact pancreatic β-cell function, adipose tissue uptake, and lipid metabolism. Furthermore, we will elucidate the mechanistic functions of GIP and its receptors in relation to other clinical conditions like cardiovascular diseases, non-alcoholic fatty liver diseases, neurodegenerative diseases, and renal disorders. Additionally, this chapter will shed light on the latest advancements in pharmacological management for T2DM, highlighting potential structural modifications of GIP and the repurposing of drugs, while also addressing the challenges involved in bringing GIP-based treatments into clinical practice. Show less