Therapeutic cargo, such as small molecule drugs, proteins and nucleic acids, can only fulfill their function in an effective way if they reach their biological target site intact and at sufficiently high concentrations. To facilitate and steer this transport process after administration and mitigate limited solubility and/or stability, the therapeutic cargo can be encapsulated into nanocarriers. These nanocarriers need to function in highly complex and crowded biological media and the journey...
Corticosteroids, such as dexamethasone, are clinically used in intravitreal injections for the treatment of inflammatory and age-related ocular diseases; however, frequent injections can cause complications. To prolong the retention of dexamethasone in the eye after intravitreal administration, sustained-release drug delivery systems have previously been investigated. The aim of this study was to evaluate the in vivo release of dexamethasone from a self-healing thermosensitive hydrogel...
Quality attributes (QAs) of monoclonal antibody (mAb) therapeutics can be jeopardized when exposed to stress factors during administration, potentially leading to patient safety risks. Therefore, strict product handling instructions are provided by the manufacturer. However, because of variations in available supplies and local guidelines, there is a need for broadened handling options in clinical setting, to improve logistics and reduce costs and shortages. Therefore 3^(rd) parties (parties...
CRISPR gene therapy holds the potential to cure a variety of genetic diseases by causing a targeted DNA break, which is repaired by host DNA damage responses. One option to introduce precise gene corrections is via the homology-directed repair (HDR) pathway. The problem in utilizing this pathway is that CRISPR-induced double stranded DNA breaks are more likely to be erroneously repaired by the non-homologous end joining (NHEJ) pathway, which may introduce random insertions or deletions at the...
Increasing evidence implicates ceramides in the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH). However, the therapeutic potential of liver-targeted ceramide lowering remains unclear. In this study, we demonstrate that elevated ceramide levels in MASH patients and mouse models are closely associated with the activation of hepatic de novo ceramide synthesis. The analysis of human hepatic single-nucleus RNA sequencing (snRNA-seq) data revealed predominant up-regulation of...
N-Carboxyanhydride (NCA) ring-opening polymerization offers an attractive approach for the construction of polypeptides. Here, we report the synthesis of a serine NCA-functionalized monomer bearing a methylaminooxy group, enabling post-polymerization attachment of complex oligosaccharides via a neo-glycosylation reaction. It provides an attractive alternative to traditional click reactions, allowing direct conjugation of glycans with a free reducing end without requiring a reactive linker or...
The well-functioning of the neurovascular unit (NVU) is supported by the three-dimensional (3D) brain physiological microenvironment that allows for extensive neural-neural and neural-vascular interactions. This microenvironment is normally hard to create in traditional in-vitro models such as the transwell model. Organ-on-a-chip (OOC) emerges as advanced model systems by providing better physiological microenvironments. However, NVU modeling in many chip platforms has not met a full 3D...
Laser powder bed fusion is an attractive technology for 3D printing objects in a powder bed and has been explored for printing pharmaceutical dosage forms, such as tablets. Recycling of non-sintered residual powder is not well understood, but is critical to prevent economic losses and improve the sustainability of this technique. We investigated the recyclability of three pharmaceutical formulations in the context of laser powder bed fusion of tablets. Three formulations consisting of common...
High-risk pediatric neuroblastoma patients have a dismal survival rate despite intensive treatment regimens. New treatment options are thus required. Even though HLA expression in neuroblastoma is low and immune cell infiltrates are limited, the presence of tumor-infiltrating lymphocytes (TILs) is indicative of better patient survival. Here, we show that most tumor lesions contain viable immune cell infiltrates after induction chemotherapy, with high percentages of CD3^(+) T cells. We therefore...
Background/Objectives: In many parts of the world, pharmacists hold the primary responsibility for providing safe and effective pharmacotherapy. A key aspect is the availability of appropriate medicines for each individual patient. When industrially manufactured medicines are unsuitable or unavailable, pharmacists can prepare tailor-made medicines. While this principle applies globally, practices vary between countries. In the Netherlands, the preparation of medicines in pharmacies is...
