A novel platform of dendritic nanogels is herein presented, capitalizing on the self-assembly of allyl-functional polyesters based on dendritic-linear-dendritic amphiphiles followed by simple cross-linking with complementary monomeric thiols via UV initiated off-stoichiometric thiol-ene chemistry. The facile approach enabled multigram creation of allyl reactive nanogel precursors, in the size range of 190-295 nm, being readily available for further modifications to display a number of core functionalities while maintaining the size distribution and characteristics of the master batch. The nanogels are evaluated as carriers of a spread of chemotherapeutics by customizing the core to accommodate each individual cargo. The resulting nanogels are biocompatible, displaying diffusion controlled release of cargo, maintained therapeutic efficacy, and decreased cargo toxic side effects. Finally, the nanogels are found to successfully deliver pharmaceuticals into a 3D pancreatic spheroids tumor model.
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http://dx.doi.org/10.1002/adfm.201806693 | DOI Listing |
Lab Chip
August 2024
Faculty of Pharmacy, Drug Research Program, University of Helsinki, Finland.
Microfluidic flow reactors functionalized with immobilized human liver microsomes (HLM chips) represent a powerful tool for drug discovery and development by enabling mechanism-based enzyme inhibition studies under flow-through conditions. Additionally, HLM chips may be exploited in streamlined production of human drug metabolites for subsequent microfluidic organ models or as metabolite standards for drug safety assessment. However, the limited shelf life of the biofunctionalized microreactors generally poses a major barrier to their commercial adaptation in terms of both storage and shipping.
View Article and Find Full Text PDFJ Am Chem Soc
June 2024
Department of Fibre and Polymer Technology, KTH Royal Institute of Technology, Teknikringen 56-68, 100 44 Stockholm, Sweden.
Antibiotic-resistant pathogens have been declared by the WHO as one of the major public health threats facing humanity. For that reason, there is an urgent need for materials with inherent antibacterial activity able to replace the use of antibiotics, and in this context, hydrogels have emerged as a promising strategy. Herein, we introduce the next generation of cationic hydrogels with antibacterial activity and high versatility that can be cured on demand in less than 20 s using thiol-ene click chemistry (TEC) in aqueous conditions.
View Article and Find Full Text PDFChem Mater
January 2024
University of Alcala, Department of Organic and Inorganic Chemistry and Research Institute in Chemistry "Andrés M. Del Río" (IQAR), 28805 Madrid, Spain.
The emergence of antibiotic resistance is a serious global health problem. There is an incessant demand for new antimicrobial drugs and materials that can address this global issue from different angles. Dendritic hydrogels have appeared as a promising strategy.
View Article and Find Full Text PDFLab Chip
May 2021
Faculty of Pharmacy, Drug Research Program, Division of Pharmaceutical Chemistry and Technology, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), Helsinki, FI-00014, Finland.
Tissue oxygen levels are known to be critical to regulation of many cellular processes, including the hepatic metabolism of therapeutic drugs, but its impact is often ignored in in vitro assays. In this study, the material-induced oxygen scavenging property of off-stoichiometric thiol-enes (OSTE) was exploited to create physiologically relevant oxygen concentrations in microfluidic immobilized enzyme reactors (IMERs) incorporating human liver microsomes. This could facilitate rapid screening of, for instance, toxic drug metabolites possibly produced in hypoxic conditions typical for many liver injuries.
View Article and Find Full Text PDFFASEB J
March 2021
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
The liver plays a central role in glucose homeostasis and hepatic insulin resistance constitutes a key feature of type 2 diabetes. However, platforms that accurately mimic human hepatic glucose disposition and allow for rapid and scalable quantification of glucose consumption dynamics are lacking. Here, we developed and optimized a colorimetric glucose assay based on the glucose oxidase-peroxidase system and demonstrate that the system can monitor glucose consumption in 3D primary human liver cell cultures over multiple days.
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