Rodent Diets Incorporated with Live Biotherapeutic Products (LBPs): An Innovative Dosing Strategy to Support Preclinical Animal Studies on LBP Intervention

Abstract

Currently, the administration of live biotherapeutic products (LBPs) in animal-based pre-clinical studies is achieved via oral gavage or voluntary consumption through the water supply. Oral gavage provides the most accurate and precise dosing for the administration of LBPs to laboratory animals; however, it induces stress responses and is labor-intensive, especially when long-term dosing is needed, placing a significant burden on both lab personnel and the subject animals. On the other hand, voluntary LBP consumption through water supply requires less effort and reduces animal stress, but still puts challenges concerning uncontrolled dosing, variations in LBP viability during the dosing period, uneven dosing due to sedimentation of LBPs, and the need for frequent refreshments due to stability and viability concerns in an aqueous environment. To address these problems, we developed lyophilized rodent diet pellets incorporated with stabilized Bioengineered Probiotic Yeast Medicines (BioPYM™), with customizable pellet size, robust mechanical strength, low friability, uniform BioPYM distribution, and proved stability for 10 weeks at 4 to 8°C storage, ensuring easy handling and more reliable dosing. Optimal cell viability preservation in dry diets was achieved through optimization of lyoprotectant and blending methods. Pharmacokinetic studies of the shedding of live BioPYM cells and their therapeutic payloads revealed the effective delivery of therapeutic agents targeting rodent gastrointestinal system. Overall, BioPYM-diet pellets represent an improved method for the delivery of LBP, and provide convenient and precise dosing. In addition, this method improves laboratory animal welfare and decreases laboratory workload.

Graphical Abstract