Biodistribution and efficacy studies of biodegradable polymer nanoparticles encapsulating anticancer drugs
Anticancer drug delivery through biodegradable nanoparticles (NPs), triggered to release their content in the vicinity of the tumor is supposed to enhance the local concentration of drugs and to reduce the side effects. The incorporation of selectively chemically degradable linkages into polymer-based NPs and microparticulate drug-delivery systems allows one to achieve external stimulus-triggered polymer degradation and triggered release (Wu et al, RSV Adv, 5:3523, 2015; Cho et al, Chem Commun, 48:6043, 2012; Petrova et al, Polym Chem, 5:3884, 2014). This is a very useful feature both to release the therapeutic cargo and to eliminate the biomaterial from the body after the cargo is released and the carrier is no longer needed. Such an external stimulus may be an enzymatic removal of protecting groups, a pH change, light or more recently, the presence of reactive oxygen species (ROS) in the surrounding environment (Chen et al, Chem Commun, 50:9714, 2014; Pu et al, ACS Nano, 8:1213, 2014; Lee et al, Nat Matr, 10:765, 2007)
We have developed a variety of NPs, which can be activated by different external stimulus. The NPs have been tested for their physiological characteristics and uptake/drug release in cell culturesand it is then necessary to test the efficacy in vivo. We are now in the process of selecting the most promising variants of bio-distribution and efficacy testing in mouse models.
220 athymice nude mice will be used to investigate biodistribution, MTD and if it will inhibit tumor growth.
For the mice in the treatment experiment it will be Lett belastende . The mice will be given sc and iv injection, but they are few and quickly performed. The mice will also be handled (fysisk fengsling) to measure the tumor size but this is also quickly done. For the mice used to find MTD the experiment will be betydlig belastende. In order to find MTD some mice might get a dose higher than what is tolerable, and can then show adverse effects. When this is observed the mice will be sacrificed so that the suffering will be as short as possible.
Reduction: we have tried to use as low number of animals as possible, but still get good results.
Replacement: in vitro experiments have been performed, and we now have to investigate in vivo as well to see if this is something that might be used in patients.
Refinement: the mice get paper and houses, to get something to play with.
We have developed a variety of NPs, which can be activated by different external stimulus. The NPs have been tested for their physiological characteristics and uptake/drug release in cell culturesand it is then necessary to test the efficacy in vivo. We are now in the process of selecting the most promising variants of bio-distribution and efficacy testing in mouse models.
220 athymice nude mice will be used to investigate biodistribution, MTD and if it will inhibit tumor growth.
For the mice in the treatment experiment it will be Lett belastende . The mice will be given sc and iv injection, but they are few and quickly performed. The mice will also be handled (fysisk fengsling) to measure the tumor size but this is also quickly done. For the mice used to find MTD the experiment will be betydlig belastende. In order to find MTD some mice might get a dose higher than what is tolerable, and can then show adverse effects. When this is observed the mice will be sacrificed so that the suffering will be as short as possible.
Reduction: we have tried to use as low number of animals as possible, but still get good results.
Replacement: in vitro experiments have been performed, and we now have to investigate in vivo as well to see if this is something that might be used in patients.
Refinement: the mice get paper and houses, to get something to play with.