A novel semi-solid pill for stress-free voluntary oral drug administration in experimental rodents

During compound screening and drug development, long-term oral drug administration to experimental rodents is often required. Oral gavage, a straightforward drug dosing technique, is not suitable for extended treatments considering the recurrent traumatic complications (gastroesophageal injury) and physiological distress (corticosterone levels alterations) that frequently bias experimental design outcomes. These reasons create a challenge for preclinical drug assays and stress-free/metabolic-inert alternatives of oral drug administration are warranted. Herein, it is presented an innovative semi-solid pill optimized to overcome aforementioned drawbacks. After a brief training period, C57BL/6 mice submitted to a chronic oral administration protocol (50 days) displayed a high index of voluntary acceptance of emptyand drug- (e.g. sitagliptin) incorporated vehicle in both healthy and CNS-diseased states. This protocol operates in a pair-housed animal housing fashion, allowing animal socialization throughout entire protocol. At the end of experiments, a normal neurobehavioral phenotype (anxiolytic, memory, locomotion parameters) was recorded. Moreover, this new methodology proved to be safe, preserving serum metabolic (glucose, triglycerides, total cholesterol), hepatic (albumin, total proteins) and renal (urea, creatinine, uric acid) parameters along with normal ileum contractility. Remarkably, coherent sitagliptin ( 10 mg/ml) plasma levels were detected, along with a robust decrease ( 80%) on the activity of its target (dipeptidyl peptidase- 4), unequivocally proving in vivo drug efficacy. Overall, this innovative approach may enclose a breakthrough advance for translational studies in scientific and pharmaceutical fields, providing a reproducible, efficient, metabolic inert and stress-free alternative for voluntary oral drug administration, with expected improvement on the data feasibility.info:eu-repo/semantics/publishedVersio