title: Accumulated polymer degradation products as effector molecules in cytotoxicity of polymeric nanoparticles.
abstract: Polymeric nanoparticles (PNPs) are a promising platform for drug, gene, and vaccine delivery. Although generally regarded as safe, the toxicity of PNPs is not well documented. The present study investigated in vitro toxicity of poly-ε-caprolactone, poly(DL-lactic acid), poly(lactide-cocaprolactone), and poly(lactide-co-glycide) NPs and possible mechanism of toxicity. The concentration-dependent effect of PNPs on cell viability was determined in a macrophage (RAW 264.7), hepatocyte (Hep G2), lung epithelial (A549), kidney epithelial (A498), and neuronal (Neuro 2A) cell lines. PNPs show toxicity at high concentrations in all cell lines. PNPs were efficiently internalized by RAW 264.7 cells and stimulated reactive oxygen species and tumor necrosis factor-alpha production. However, reactive nitrogen species and interleukin-6 production as well as lysosomal and mitochondrial stability remained unaffected. The intracellular degradation of PNPs was determined by monitoring changes in osmolality of culture medium and a novel fluorescence recovery after quenching assay. Cell death showed a good correlation with osmolality of culture medium suggesting the role of increased osmolality in cell death.
authors: * Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab 160 062, India.
authors: Raman Preet
authors: RP
authors: Singh
authors: Poduri
authors: P
authors: Ramarao
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009994:Osmolar Concentration; D011091:Polyesters / Q000633:toxicity; D011098:Polyglactin 910 / Q000633:toxicity; D011108:Polymers / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D011091:Polyesters; D011108:Polymers; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C016240:polycaprolactone; D011098:Polyglactin 910; C062968:lactide-caprolactone copolymer
keywords: dye release; in vitro toxicity; intracellular degradation; nanoparticle degradation; osmotic pressure; poly(DL-lactic acid); poly(lactide-co-glycide); poly(lactide-cocaprolactone); poly-ε-caprolactone; polymeric nanoparticles