Abstract
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.
Highlights
Design and exploration of a variety of engineered nanoparticles (NPs) such as polymers, inorganic materials, hybrid composites etc. for diverse biomedical applications such as drug carriers/therapeutic agents in disease therapy, magnetic resonance contrasts in diagnosis/imaging etc. has improved considerably in recent years (Raffaele Conte et al, 2018)
PEG-PLA NP systems have been emerging as a revolutionary carrier establishment of drug delivery, therapy and diagnosis
This study demonstrated the biodistribution pattern of PEG-PLA NPs following i.v. and oral routes of administration in mice and the influence of administration route on induction of oxidative stress, DNA damage, hematological and histopathological effects of PEG-PLA NPs
Summary
Design and exploration of a variety of engineered nanoparticles (NPs) such as polymers, inorganic materials, hybrid composites etc. for diverse biomedical applications such as drug carriers/therapeutic agents in disease therapy, magnetic resonance contrasts in diagnosis/imaging etc. has improved considerably in recent years (Raffaele Conte et al, 2018). PEG-PLA NP systems have been emerging as a revolutionary carrier establishment of drug delivery, therapy and diagnosis In these NPs, generally PLA forms the core and PEG forms the corona, thereby protecting the NPs from aggregation. Further support is provided by the successful use of PEGylated long circulating nano-objects for therapeutic applications These include the commercialization of (i) PEGylated liposomal doxorubicin (Doxil®/Caelyx®), (ii) PEG-PLA micellar formulation, Genexol-PM (an anticancer agent paclitaxel loaded micelles) for the treatment of metastatic or recurrent breast cancer, and locally advanced or metastatic non-small cell lung cancer as first-line therapy (Reddy & Bazile., 2014b), while the docetaxel-loaded PEG-PLA NPs formulation, BIND014, intended for treatment of metastatic castration-resistant prostate cancer (mCRPC) is currently in clinical testing (Autio et al, 2018). It is essential to attain a thorough knowledge on the biodistribution of PEG-PLA NPs, their interaction with the biological components, the resulting implications at the molecular and genetic levels to assess the NPs safety levels for the intended application
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