Influence of Administration Route and Dose on Biodistribution Profile and Effects of PEG-PLA Nanoparticles in Mice

Polyethylene glycol-polylactic acid nanoparticles (PEG-PLA NPs) represent a new generation of parenteral therapeutics systems. Following administration, these NPs possess the potential to interact with biological machinery. Therefore, it is essential to get a systematic understanding of the biological fate of these NPs to evaluate their safety. In the present study, two doses (20 and 40 mg/kg) of technetium-99m labeled PEG-PLA NPs were administered intravenous (i.v.) and oral into mice and the distribution was assessed at 1, 2, 4 and 24 h post administration. Biodistribution and blood kinetic profiles revealed the extended systemic circulation of the NPs. Dose-dependent presence of NPs (p<0.05) was detected in the blood, liver, lung, spleen, and kidney of i.v. injected mice, and also in the blood, lung, spleen, stomach, and intestine of oral administered mice. The consequences of NP interaction with the biological components were studied by measurement of hematology, oxidative stress, genotoxic and histological parameters. Significantly increased levels of oxidative stress markers such as glutathione were observed in the liver, and spleen of i.v. injected mice and liver, stomach, and intestine of orally treated mice. Decreased lipid peroxidation levels (p<0.05) were observed in the liver of orally treated mice versus untreated mice. Even though PEG-PLA NPs have been shown to induce oxidative DNA damage, interestingly no histological lesions were observed in selected organs except lung of i.v. treated mice, which showed moderate vascular congestion. Such insights on in vivo distribution and understanding of nano-bio interactions at molecular and genetic levels are considered fundamental for the designing of safer nanoparticles for biomedical applications.