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Owing to the scope and aims of the current discussion paper, the in vitro and in vivo preclinical studies are summarised briefly in appendix 1 and include cytotoxicity assessments in a number of primary cells and cell lines and toxicological studies in rats and mice

The better effect of LCLN than LC was evidenced by the findings of earlier studies 92,100 , likely due to physical attributes (including shape, size, and zeta potential), alongside enhancements in encapsulation efficiency, drug content, drug loading capacity, drug release, and in vitro release of the formulated LC-SLNs, all of which were optimized in the niosomal form 19

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Importantly, many of the pathways demonstrated to be altered by metformin treatment in this study, including cell cycle and cell death are dependent on cellular metabolism, indicating a potential role for altered energy metabolism as a master regulator of radioresistance in rectal cancer

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