CsA formulated in migliol oil delayed corneal rejection onset, but blood levels were evident in this group. CsA loaded-nanocapsules showed no effect on rejection and the drug was not detectable in blood. These data, along with the current concepts on corneal graft rejection immunology, suggest that the immunomodulatory effect of topical CsA in the prevention of corneal graft rejection may be systemically-mediated.
Around 95% of anti-cancer drugs that show promise during preclinical study fail to gain FDA-approval for clinical use. This failure of the preclinical pipeline highlights the need for improved, physiologically-relevant in vitro models that can better serve as reliable drug-screening tools. The vascularized micro-tumor (VMT) is a novel three-dimensional model system that recapitulates the complex human tumor microenvironment, including perfused vasculature, within a transparent microfluidic device, allowing real-time study of drug responses and tumor-stromal interactions. Here we have validated the VMT platform for the study of colorectal cancer (CRC), the second leading cause of cancer-related deaths, by showing that gene expression, tumor heterogeneity, and treatment response in the VMT more closely model CRC tumor clinicopathology than current standard drug screening modalities, including 2-dimensional (2D) monolayer culture and 3dimensional (3D) spheroids.
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