Providing animal data for the development of in silico biodistribution algorithm development 2
1 Formål
To perfome a biodistribution study of a nanoformulated drug (cabazitaxel). The data will be used as an input function to a data model of biodistribution of nanomedicine. This model will hopefully reduce the cost and use of animals in future studies. In this second study, we will complement data from FOTS 21915 by including different concentrations of the drug in order to investigate dose/linerarity. This will increase the data for the input function. Additionally, we will perform hematology and clinical chemistry in order to correlate biodistribution data to toxicological response. We will also include a newly developed method to analyze the constituents of the nanoparticle and thereby increase the understanding of drug distribution compared to particle distribution.
2 Skadevirkninger
The animals will be given a cytostatic drug, but only one dose. We foresee some weight loss (5-10%) from the treatment, but animals recover their weight within one week. The study is graded as moderate severity due to the potential weight loss.
3 Forventet nytteverdi
Reduction of use of animals and cost when developing nanomedicine. Increased understanding of the biodistribution, pharmacokinetics and how it drives toxicity.
4 Antall dyr og art
Rattus Norwegicus (Wistar) 46 st
5 Hvordan etterleve 3R
The groups are kept relatively small but the samples collected for analysis will be close to 500. The animals used have free access to food, drinking water and environmental enrichment.
To perfome a biodistribution study of a nanoformulated drug (cabazitaxel). The data will be used as an input function to a data model of biodistribution of nanomedicine. This model will hopefully reduce the cost and use of animals in future studies. In this second study, we will complement data from FOTS 21915 by including different concentrations of the drug in order to investigate dose/linerarity. This will increase the data for the input function. Additionally, we will perform hematology and clinical chemistry in order to correlate biodistribution data to toxicological response. We will also include a newly developed method to analyze the constituents of the nanoparticle and thereby increase the understanding of drug distribution compared to particle distribution.
2 Skadevirkninger
The animals will be given a cytostatic drug, but only one dose. We foresee some weight loss (5-10%) from the treatment, but animals recover their weight within one week. The study is graded as moderate severity due to the potential weight loss.
3 Forventet nytteverdi
Reduction of use of animals and cost when developing nanomedicine. Increased understanding of the biodistribution, pharmacokinetics and how it drives toxicity.
4 Antall dyr og art
Rattus Norwegicus (Wistar) 46 st
5 Hvordan etterleve 3R
The groups are kept relatively small but the samples collected for analysis will be close to 500. The animals used have free access to food, drinking water and environmental enrichment.