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Tendinopathy involves the inflammation and degeneration of the tendon due to repetitive strain injury. Current treatments primarily target inflammation resolution, yet they do not aim at tissue regeneration. In this study, a microfluidics approach is harnessed to develop a platform of lipid nanoparticles (LNPs) loaded simultaneously with SMAD3 siRNA and collagen I mRNA, aiming to explore its potential dual antifibrotic and regenerative effects in human tenocytes. The developed LNPs displayed size homogeneity and colloidal stability and exhibited high cytocompatibility in human tenocytes. Moreover, LNPs allowed for efficient uptake and transfection efficiency of the RNAs. In the in vitro efficacy studies, the gene expression and production of SMAD3 and collagen I were tested by real-time quantitative chain polymerase reaction and immuno- and intracellular staining, revealing collagen I production enhancement, SMAD3 inhibition, and modulation of other tendon repair factors by the LNPs. Overall, the potential of this platform of RNA-loaded LNPs to be used as a dual therapeutic approach to prevent fibrosis and promote tissue remodeling in late stages of tendon diseases was confirmed. [ABSTRACT FROM AUTHOR]

A pioneering approach in the domain of transdermal drug delivery systems (TDDS) is introduced by using microneedles (MNs) fabricated from an amorphous solid dispersion comprising only a model drug and an amphiphilic block copolymer to form a drug nanoformulation upon MN dissolution. To maximize drug loading and ensure consistent release, a minimalist formulation that achieves 40 wt% drug loading, which is a significant improvement over existing methods, is developed. Using scanning electron microscopy, the morphology of MNs is examined across a spectrum of drug loading ratios, demonstrating the consistency in structure and integrity. Mechanical testing confirms the MNs' proficiency in effective skin penetration. A comparative study on the formation of polymeric micelles underscores the innovative concept of a “nano‐in‐micro drug delivery system”. The results demonstrate that MNs manufactured from an amorphous solid dispersion of drug and amphiphilic block copolymer with ultra‐high loading enhance the availability and release dynamics of hydrophobic drugs, positioning them as a tool for enhancing TDDS. This study sets a new benchmark in the utilization of polymer‐drug nanoformulations for transdermal applications and underscores the capacity for high drug loading and the creation of adaptable drug delivery mechanisms for the studied amphiphilic block copolymer. [ABSTRACT FROM AUTHOR]

Summary: The authors examine several reports of the literature concerning thyrotoxic dilated cardiomyopathy. In particular, it is pointed out that this clinical manifestation of hyperthyroidism is rare in readily diagnosed and properly treated hyperthyroidism. Case reports are analyzed comparatively. A case deriving from the direct experience of the authors is also presented., Learning Points: Dilated cardiomyopathy has been reported as the initial presentation of hyperthyroidism in only 6% of patients although <1% developed severe LV dysfunction. Clinical picture of thyrotoxic dilated cardiomyopathy can degenerate into an overt cardiogenic shock sometimes requiring the use of devices for mechanical assistance to the circulation, or extracorporeal membrane oxygenation. For thyrotoxic dilated cardiomyopathy, evidence-based pharmacologic measures valid for heart failure should always be supplemented by the administration of specific thyroid therapies such as thionamides (methimazole, carbimazole or propylthiouracil), whose relatively long latency of action should be supported by the i.v. administration of small doses of beta-blocker. In cases of cardiogenic shock, the administration of beta-blocker should be carried out only after the restoration of satisfactory blood pressure levels- with the prudent use of synthetic catecholamines, if necessary.