Many macromolecular therapeutics could potentially treat genetic disorders and cancer. They have, however, not yet reached the clinical stage owing to a lack of suitable carriers that can bring the therapeutics from the administration site to the subcellular site in target cells. One of the reasons that is hindering the development of such carriers is the limited knowledge of their transport dynamics and intracellular processing. Single-particle tracking (SPT) microscopy, thanks to its single molecule sensitivity and its broad applicability, has found its entry in the field of drug delivery to get an answer to these questions. This review aims to introduce the fundamentals of SPT to the drug delivery community and highlight the most recent discoveries obtained with SPT in the field of drug delivery.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.2217/nnm.14.43 | 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.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!