3 Minute 3Rs March 2020
[NC3Rs] Nanomedicines have many potential advantages, including their ability to home to specific diseased tissues and exert a localised effect. Due to their relatively large size, the biodistribution of nanomedicines does not follow the same rules as small molecules and is largely dictated by the diameter of the blood vessels they pass through en route to their target tissue. This means that although current methods to assess biodistribution rely heavily on the use of animals including rodents and non-human primates, the results can vary greatly between preclinical species and man. Using an in vitro cell based model of nanoparticle uptake to build a computer simulation, Edward Price and colleagues at the University of Central Florida have developed a predictive system to replace animal use for determining nanomedicine PKPD. The model takes account of blood vessel size, tissue-specific porosity and the kinetics of distribution to cellular and paracellular compartments. By being able to better predict where nanomedicines will end up in the body, scientists can design safer and more effective drugs based on nanomaterials without using animals to assess biodistribution. For more information on their study, see the paper linked in the podcast description.
[NA3RsC] Human safety is a key priority when developing new drugs. Toxicity testing often requires drugs to be used in animal models before human clinical trials. Historically, toxicology testing has involved two species: one rodent and one non-rodent. However, in some cases, only 1 animal species is used successfully. This month, an international working group of 37 diverse organizations led by Dr. Helen Prior published a paper on this topic in Regulatory Toxicology and Pharmacology. They reviewed data from 172 potential new drugs, across a wide range of small molecules and vaccines. These potential new drugs were tested in either 1 or 2 species. The working group found that often when 2 species were used they showed similar toxicity profiles in both. Therefore, it may be possible to reduce the number of species new drugs are tested in while maintaining human safety.
[LA]. Social housing is generally recommended for social species, such as the mouse, whenever possible. But housing animals together can lead to incidences of aggression – an unwanted outcome for the welfare of the animals involved. Female mice tend to get along just fine, but males can sometimes be another story. In a new 14 week study measuring aggression and physical signs of well-being in male Cd-1 mice, a stock with an aggressive reputation, Paulin Jirkof and colleagues consider three variables that might influence how well those animals get along: group size, the age at which males are allocated to their groups, and handling frequency. The full results can be found in the journal Scientific Reports but overall levels of aggression were actually low. And for these mice, three was not a crowd. Trios got on better than pairs, with solo males scoring the lowest on measures of well-being.
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