Mutations in the gene encoding Lamin B receptor (LBR), a nuclear-membrane protein with sterol reductase activity, have been linked to rare human disorders. Phenotypes range from a benign blood ...disorder, such as Pelger-Huet anomaly (PHA), affecting the morphology and chromatin organization of white blood cells, to embryonic lethality as for Greenberg dysplasia (GRBGD). Existing PHA mouse models do not fully recapitulate the human phenotypes, hindering efforts to understand the molecular etiology of this disorder. Here we show, using CRISPR/Cas-9 gene editing technology, that a 236bp N-terminal deletion in the mouse Lbr gene, generating a protein missing the N-terminal domains of LBR, presents a superior model of human PHA. Further, we address recent reports of a link between Lbr and defects in X chromosome inactivation (XCI) and show that our mouse mutant displays minor X chromosome inactivation defects that do not lead to any overt phenotypes in vivo. We suggest that our N-terminal deletion model provides a valuable pre-clinical tool to the research community and will aid in further understanding the etiology of PHA and the diverse functions of LBR.
Growing demand for customized pharmaceutics and medical devices makes the impact of additive manufacturing increased rapidly in recent years. The 3D printing has become one of the most revolutionary ...and powerful tool serving as a technology of precise manufacturing of individually developed dosage forms, tissue engineering and disease modeling. The current achievements include multifunctional drug delivery systems with accelerated release characteristic, adjustable and personalized dosage forms, implants and phantoms corresponding to specific patient anatomy as well as cell-based materials for regenerative medicine. This review summarizes the newest achievements and challenges of additive manufacturing in the field of pharmaceutical and biomedical research that have been published since 2015. Currently developed techniques of 3D printing are briefly described while comprehensive analysis of extrusion-based methods as the most intensively investigated is provided. The issue of printlets attributes, i.e. shape and size is described with regard to personalized dosage forms and medical devices manufacturing. The undeniable benefits of 3D printing are highlighted, however a critical view resulting from the limitations and challenges of the additive manufacturing is also included. The regulatory issue is pointed as well.
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Three-dimensional printing is one of the fastest developing technology within pharmaceutical field. With many advantages this method can be found as a new dosage form manufacturing ...technique, however low printing efficiency stays as one of the major limitations. Therefore, the preparation of filaments as a feedstock and printing of the final dosage forms in pharmacies may by the direction of development for this method. Thus, simple dosage and dissolution profile modification seems to be essential. This can be done in simple way by addition drug-free filament during printing process. In this work the influence of dual co-extrusion process on the properties of 3D-printed tablets with aripiprazole was evaluated. A ZMorph® 3D printer equipped with DualPro extruder was employed to produce tablets made from Kollicoat® IR aripiprazole-loaded filament and commercially available PLA filament used to modify the release profile. Optical and polarized light microscopy were utilized to evaluate structure of printed objects and X-ray diffraction studies were performed to determine crystallinity of aripiprazole within filament and tablets. Fast dissolution of aripiprazole resulted from its amorphization while prolonged drug release was a result of co-extrusion with PLA filament. Importantly, the drug remained crystalline within the filament and phase transition into disordered system appeared during printing of tablets. Given the high stability of crystalline materials such feature is especially beneficial for long-term storage of feedstock filament.
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