The aim of this study was to assess the critical quality attributes of parenteral nanoemulsion formulations by measuring several physicochemical parameters and linking them to their in vitro performance, illustrating how simplistic and routinely used approaches are insufficient for understanding a potential nanomedicine. Physicochemical characterization should encompass size and size distribution through at least two orthogonal techniques, such as dynamic light scattering (DLS) and electron microscopy, with added value from analytical ultracentrifugation. In vitro toxicity assessment was performed using three different assays to determine mitochondrial activity (WST-1), membrane integrity (lactate dehydrogenase release (LDH) assay), and cell viability (propidium iodide (PI) staining).
View Article and Find Full Text PDFGlioblastoma (GBM) is an aggressive brain cancer with a highly immunosuppressive tumor microenvironment (TME), invariably infiltrated by tumor-associated macrophages (TAMs). These TAMs resemble M2 macrophages, which promote tumor growth and suppress immune responses. GBM cells secrete extracellular vesicles (EVs) containing microRNA-25, which inhibits the cGAS-STING pathway and prevents TAMs from adopting a pro-inflammatory M1 phenotype.
View Article and Find Full Text PDFOsteoarthritis (OA) is a joint disease common worldwide. Currently, no disease-modifying osteoarthritis drugs (DMOADs) have successfully passed clinical trials, often due to a lack of cartilage penetration. Thus, targeting the extracellular matrix (ECM) is a major priority.
View Article and Find Full Text PDFMesenchymal stem cell (MSC) therapy shows promise in regenerative medicine. For osteoarthritis (OA), MSCs delivered to the joint have a temporal window in which they can secrete growth factors and extracellular matrix molecules, contributing to cartilage regeneration and cell proliferation. However, upon injection in the non-vascularized joint, MSCs lacking energy supply, starve and die too quickly to efficiently deliver enough of these factors.
View Article and Find Full Text PDFIt is well known that protein corona affects the "biological identity" of nanoparticles (NPs), which has been seen as both a challenge and an opportunity. Approaches have moved from avoiding protein adsorption to trying to direct it, taking advantage of the formation of a protein corona to favorably modify the pharmacokinetic parameters of NPs. Although promising, the results obtained with engineered NPs still need to be completely understood.
View Article and Find Full Text PDF