Joshua Reineke, Ph.D., assistant professor of pharmaceutical sciences in the Eugene Applebaum College of Pharmacy and Health Sciences, examined how a biodegradable polymer particle - polylactic-co-glycolic acid (PLGA) -breaks down in live tissue.
He believes the potential impact of his work is broad, as nanoparticles have increasingly been developed as carriers of drug treatments for diseases and as imaging agents; they are also used in numerous consumer products.
The kinetics of nanoparticle biodegradation is an important factor that can control how and where a drug is released, impacting treatment efficacy as well as potential toxicity to non-target tissues from nanoparticle exposure.
‘If nanoparticles given to a patient release a drug before particles can ever get to target tissue, then we get high toxicity and low effect,’ Reineke said in a statement. ‘Conversely, if particles are drawn to a tissue but don’t release the drug until long afterward, then we also don’t get the therapeutic effect.’
Much previous research has studied nanoparticle biodegradation in vitro, but Reineke and the study’s lead author, Abdul Khader Mohammad, Ph.D., a recent WSU graduate, believe they are the first to quantify biodegradation rates after systemic administration.
Their study, Quantitative Detection of PLGA Nanoparticle Degradation in Tissues following Intravenous Administration, was published in the journal Molecular Pharmaceutics.
Keeping concentration levels the same, Reineke and Mohammad administered PLGA as particles in sizes of 200nm and 500nm intravenously in mice, an important administration route of nanomedicines for cancer applications, and measured the quantity of the nanoparticles in all tissues and the rates at which it degraded. They then compared those rates to those predicted by in vitro measurements.
Reineke said the 200nm particles degraded much faster in the body than in vitro, while the 500nm particles degraded similarly to in vitro analyses. The liver and spleen had the highest concentration of polymers and were easiest to analyse.
Researchers found that 500nm particles degraded faster in the liver than the spleen, but for the 200nm size the degradation rate in the liver and the spleen were similar.
‘It’s known that larger particles degrade differently, and we verified that but they didn’t quite degrade in vivo the way we would expect,’ Reineke said. ‘We found that among tissue types there are differences in how they degrade.’
‘That tells us that in vitro degradation doesn’t predict in vivo degradation very well, because we see so many differences.’
Reineke said that by in vivo testing of other types of nanoparticles, a mathematical model can be developed to help determine which are most effective and have the lowest toxicity for a given application.