In photodynamic therapy (PDT), photosensitizers are required to arrive in high concentrations at selective targets like cancer cells avoiding toxicity in healthy tissue. In this work, we propose the application of porous calcium carbonate carriers in the form of polycrystalline vaterite for this task. We investigated the loading efficiency for the photosensitizer Photosens in vaterite micro- and nanocarriers. A possible release mechanism depending on the surrounding pH was studied, showing a fast degradation of the carriers in buffers below pH7. These results hold out the prospect of a novel PDT drug delivery system. Variation of particle size or additional coatings allow custom-design of workload release curves. An intrinsic cancer-sensitivity can be expected from the pH-dependent release in the acidic microenvironment of cancer tissue.
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http://dx.doi.org/10.1016/j.bpc.2013.07.006 | 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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