Assessment Of The Biological Effects Of Multifunctional Nano-drug-carrier And Its Encapsulated Drugs

Nanoparticle encapsulated doxorubicin (DOX) and paclitaxel (TAX) have the potential for novel therapeutic use to against cancer in the clinic. However, the safety of the nanoparticle material, namely methoxypoly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA), has not been fully studied for its biological effects for use as a multifunctional drug carrier. In addition, the effects of mPEG-PLGA on the actions of the free drugs that they packaged are far from been fully elucidated. We have applied NMR-based metabonomics methodology in order to characterize and analyze the systemic metabolic changes in mice after exposed to mPEG-PLGA, mPEG-PLGA encapsulated DOX and TAX (NP-D/T) and their free forms. The results show that mPEG-PLGA exposure acts as a transient stimulus towards the host rather than inducing any severe adverse effect, which supports the safety of blank mPEG-PLGA as a drug delivery system. In addition, mPEG-PLGA encapsulated drug DOX and TAX is less toxic than their free form drugs, which particularly manifested in the reduction toxicity in heart and liver, but not the spleen of mice. Furthermore, NP-D/T and their free forms induce a shift in energy metabolism, stimulate anti-oxidation of system and disturb the gut microbial activity of the host. These findings provide a holistic insight into the biological effects of polymer nanoparticles and nanoparticle encapsulated drugs. This study also furthers our understanding of the mechanisms involved in the modification effects of mPEG-PLGA packaging at a molecular level.