Porous silicon nanoparticles (PSiNPs) are attractive carriers for targeted drug delivery in nanomedicine. For in vivo applications, the biodegradation property of PSiNPs provides a pathway for their safe clearance from the body. Particles sizes of 80-120 nm are of particular interest as they are important for cellular applications, such as drug delivery for cancer therapy, because these nanoparticles can take advantage of the enhanced permeability and retention effect to deliver drug preferentially to tumors with leaky vasculature, yet large enough to avoid renal clearance. However, the biodegradability rate of such particles is often too fast, which limits particle half-life and potentially reduces their in vivo delivery efficiency. In this work, we focus on the degradation of nanoscale particles and study the effect of both thermal oxidation and silica coating on the stability of PSiNPs in phosphate buffered saline solution (a close mimic of a basic biological fluid). Using thermal oxidation, the half-life of PSiNPs can be varied from 10 min up to 3 h. Using silica coating, the half-life can be extended further to 8 h. The particles produced using both these techniques can be functionalized using standard silica surface chemistries developed for applications in drug delivery.
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http://dx.doi.org/10.1002/jbm.a.34294 | DOI Listing |
Mol Pharm
January 2025
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
Microneedles (MNs) are emerging as versatile tools for both therapeutic drug delivery and diagnostic monitoring. Unlike hypodermic needles, MNs achieve these applications with minimal or no pain and customizable designs, making them suitable for personalized medicine. Understanding the key design parameters and the challenges during contact with biofluids is crucial to optimizing their use across applications.
View Article and Find Full Text PDFJMIR Res Protoc
January 2025
Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
Background: Although existing disease preparedness and response frameworks provide guidance about strengthening emergency response capacity, little attention is paid to health service continuity during emergency responses. During the 2014 Ebola outbreak, there were 11,325 reported deaths due to the Ebola virus and yet disruption in access to care caused more than 10,000 additional deaths due to measles, HIV/AIDS, tuberculosis, and malaria. Low- and middle-income countries account for the largest disease burden due to HIV, tuberculosis, and malaria and yet previous responses to health emergencies showed that HIV, tuberculosis, and malaria service delivery can be significantly disrupted.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States.
PROTACs usually occupy physicochemical space outside the one defined by classical drug-like molecules, which often presents considerable challenges in their optimization and development for oral administration. We have previously reported phenyl glutarimide (PG)-based BET PROTAC SJ995973, with improved overall degradation and antiproliferative activities compared to its direct thalidomide-based analogue dBET1, but similarly poor pharmacokinetic profile. To further demonstrate the PG utility, we describe here optimization efforts that led to the discovery of an orally bioavailable BET-PROTAC SJ44236 (), and results of a comprehensive comparative study with analogues containing alternative CRBN-directing warheads.
View Article and Find Full Text PDFSci Transl Med
January 2025
College of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou 310058, China.
Macrophages play a central role in antitumor immunity, making them an attractive target for gene therapy strategies. However, macrophages are difficult to transfect because of nucleic acid sensors that can trigger the degradation of foreign plasmid DNA. Here, we developed a macrophage-specific editing (MAGE) system by which compact plasmid DNA encoding a CasRx editor can be delivered to macrophages by a poly(β-amino ester) (PBAE) carrier to bypass the DNA sensor and enable RNA editing in vitro and in vivo.
View Article and Find Full Text PDFJ Neurol
January 2025
Parkinson's Disease Research Clinic, Macquarie University, 75 Talavera Road, Sydney, NSW, 2109, Australia.
Impulse Control Disorders (ICDs) are increasingly recognized as a significant non-motor complication in Parkinson's disease (PD), impacting patients and their caregivers. ICDs in PD are primarily associated with dopaminergic treatments, particularly dopamine agonists, though not all patients develop these disorders, indicating a role for genetic and other clinical factors. Studies over the past few years suggest that the mesocorticolimbic reward system, a core neural substrate for impulsivity, is a key contributor to ICDs in PD.
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